Mixed Topics

NASHVILLE, TENN. – Supported by several cases series, a large cohort analysis has associated exposure to probiotics in the intensive care unit with a measurable increase in bacteremia and bacteremia-related mortality due to organisms in these preparations, according to new findings presented at the annual meeting of the American College of Chest Physicians (CHEST).

According to data presented by Scott Mayer, MD, chief resident at HealthONE Denver, which is part of the HCA Healthcare chain of hospitals, the risk is increased by any probiotic exposure. However, the risk is particularly acute for powdered formulations, presumably because powder more easily disseminates to contaminate central venous catheters.

“We think that probiotics should be eliminated entirely from the ICU. If not, we encourage eliminating the powder formulations,” said Dr. Mayer, who led the study.

The data linking probiotics to ICU bacteremia were drawn from 23,533 ICU admissions over a 5-year period in the HCA hospital database. Bacteremia proven to be probiotic-related was uncommon (0.37%), but the consequences were serious.

For those with probiotic-related bacteremia, the mortality rate was 25.6% or essentially twofold greater than the 13.5% mortality rate among those without probiotic bacteremia. An odds ratio drawn from a regression analysis confirmed a significant difference (OR, 2.23; 95% confidence interval, 1.30-3.71; P < .01).

“The absolute risk of mortality is modest but not insignificant,” said Dr. Mayer. This suggests one probiotic-related mortality for about every 200 patients taking a probiotic in the ICU.

These deaths occur without any clear compensatory benefit from taking probiotics, according to Dr. Mayer. There is a long list of potential benefits from probiotics that might be relevant to patients in the ICU, particularly prophylaxis for Clostridioides difficile infection, but also including a variety of gastrointestinal disorders, such as irritable bowel syndrome; however, none of these are firmly established in general, and particularly for patients in the ICU.

“The American College of Gastroenterology currently recommends against probiotics for the prevention of C. diff.,” Dr. Mayer said. Although the American Gastroenterological Association has issued a “conditional recommendation” for prevention of C. diff. infection with probiotics, Dr. Mayer pointed out this is qualified by a “low quality of evidence” and it is not specific to the ICU setting.

“The evidence for benefit is weak or nonexistent, but the risks are real,” Dr. Mayer said.

To confirm that probiotic-associated ICU bacteremias in the HCA hospital database were, in fact, related to probiotics being taken by patients at time of admission, Dr. Mayer evaluated the record of each of the 86 patients with probiotic bacteremia–associated mortality.

“I identified the organism that grew from the blood cultures to confirm that it was contained in the probiotic the patient was taking,” explained Dr. Mayer, who said this information was available in the electronic medical records.

The risk of probiotic-associated bacteremia in ICU patients was consistent with a series of case series that prompted the study. Dr. Mayer explained that he became interested when he encountered patients on his ICU rounds who were taking probiotics. He knew very little about these agents and explored the medical literature to see what evidence was available.

“I found several case reports of ICU patients with probiotic-associated infections, several of which were suspected of being associated with contamination of the central lines,” Dr. Mayer said. In one case, the patient was not taking a probiotic, but a patient in an adjacent bed was receiving a powdered probiotic that was implicated. This prompted suspicion that the cause was central-line contamination.

This was evaluated in the HCA ICU database and also found to be a significant risk. Among the 67 patients in whom a capsule or tablet was used, the rate of probiotic-associated bacteremia was 0.33%. For those in which the probiotic was a powdered formulation, the rate was 0.76%, a significant difference (P < .01).

Dr. Mayer acknowledged that these data do not rule out all potential benefits from probiotics in the ICU. He believes an obstacle to proving benefit has been the heterogeneity of available products, which are likely to be relevant to any therapeutic role, including prevention of C. diff. infection.

“There are now a large number of products available, and they contain a large variety of strains of organisms, so this has been a difficult area to study,” he said. However, he maintains it is prudent at this point to avoid probiotics in the ICU because the risks are not confined to the patient making this choice.

“My concern is not just the lack of evidence of benefit relative to the risk for the patient but the potential for probiotics in the ICU to place other patients at risk,” Dr. Mayer said.

Others have also noted the potential benefits of probiotics in the ICU, but the promise remains elusive. In a 2018 review article published in the Journal of Emergency and Critical Care Medicine, the authors evaluated a series of potential applications of probiotics in critically ill patients. These included treatment of ventilator-associated pneumonia (VAP), catheter-associated urinary tract infections (CAUTI), and surgical-site infections (SSI). For each, the data were negative or inconclusive.

Over the 4 years that have passed since the review was published, several trials have further explored the potential benefits of probiotics in the ICU but none have changed this basic conclusion. For example, a 2021 multinational trial, published in The Lancet, randomized more than 2,600 patients to probiotics or placebo and showed no effect on VAP incidence (21.9% vs. 21.3%).

The lead author of the 2018 review, Heather A. Vitko, PhD, an associate professor in the department of acute and tertiary care, University of Pittsburgh School of Nursing, also emphasized that the potential for benefit cannot be considered without the potential for risk. She, like Dr. Mayer, cited the case studies implicating probiotics in systemic infections.

For administration, probiotic capsules or sachets “often need to be opened for administration through a feeding tube,” she noted. The risk of contamination comes from both the air and contaminated hands, the latter of which “can cause a translocation to a central line catheter where the microbes have direct entry into the systemic circulation.”

She did not call for a ban of probiotics in the ICU, but she did recommend “a precautionary approach,” encouraging clinicians to “distinguish between reality [of what has been proven] and what is presented in the marketing of antibiotics.”

Dr. Mayer and Dr. Vitko have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NASHVILLE, TENN. – Supported by several cases series, a large cohort analysis has associated exposure to probiotics in the intensive care unit with a measurable increase in bacteremia and bacteremia-related mortality due to organisms in these preparations, according to new findings presented at the annual meeting of the American College of Chest Physicians (CHEST).

According to data presented by Scott Mayer, MD, chief resident at HealthONE Denver, which is part of the HCA Healthcare chain of hospitals, the risk is increased by any probiotic exposure. However, the risk is particularly acute for powdered formulations, presumably because powder more easily disseminates to contaminate central venous catheters.

“We think that probiotics should be eliminated entirely from the ICU. If not, we encourage eliminating the powder formulations,” said Dr. Mayer, who led the study.

The data linking probiotics to ICU bacteremia were drawn from 23,533 ICU admissions over a 5-year period in the HCA hospital database. Bacteremia proven to be probiotic-related was uncommon (0.37%), but the consequences were serious.

For those with probiotic-related bacteremia, the mortality rate was 25.6% or essentially twofold greater than the 13.5% mortality rate among those without probiotic bacteremia. An odds ratio drawn from a regression analysis confirmed a significant difference (OR, 2.23; 95% confidence interval, 1.30-3.71; P < .01).

“The absolute risk of mortality is modest but not insignificant,” said Dr. Mayer. This suggests one probiotic-related mortality for about every 200 patients taking a probiotic in the ICU.

These deaths occur without any clear compensatory benefit from taking probiotics, according to Dr. Mayer. There is a long list of potential benefits from probiotics that might be relevant to patients in the ICU, particularly prophylaxis for Clostridioides difficile infection, but also including a variety of gastrointestinal disorders, such as irritable bowel syndrome; however, none of these are firmly established in general, and particularly for patients in the ICU.

“The American College of Gastroenterology currently recommends against probiotics for the prevention of C. diff.,” Dr. Mayer said. Although the American Gastroenterological Association has issued a “conditional recommendation” for prevention of C. diff. infection with probiotics, Dr. Mayer pointed out this is qualified by a “low quality of evidence” and it is not specific to the ICU setting.

“The evidence for benefit is weak or nonexistent, but the risks are real,” Dr. Mayer said.

To confirm that probiotic-associated ICU bacteremias in the HCA hospital database were, in fact, related to probiotics being taken by patients at time of admission, Dr. Mayer evaluated the record of each of the 86 patients with probiotic bacteremia–associated mortality.

“I identified the organism that grew from the blood cultures to confirm that it was contained in the probiotic the patient was taking,” explained Dr. Mayer, who said this information was available in the electronic medical records.

The risk of probiotic-associated bacteremia in ICU patients was consistent with a series of case series that prompted the study. Dr. Mayer explained that he became interested when he encountered patients on his ICU rounds who were taking probiotics. He knew very little about these agents and explored the medical literature to see what evidence was available.

“I found several case reports of ICU patients with probiotic-associated infections, several of which were suspected of being associated with contamination of the central lines,” Dr. Mayer said. In one case, the patient was not taking a probiotic, but a patient in an adjacent bed was receiving a powdered probiotic that was implicated. This prompted suspicion that the cause was central-line contamination.

This was evaluated in the HCA ICU database and also found to be a significant risk. Among the 67 patients in whom a capsule or tablet was used, the rate of probiotic-associated bacteremia was 0.33%. For those in which the probiotic was a powdered formulation, the rate was 0.76%, a significant difference (P < .01).

Dr. Mayer acknowledged that these data do not rule out all potential benefits from probiotics in the ICU. He believes an obstacle to proving benefit has been the heterogeneity of available products, which are likely to be relevant to any therapeutic role, including prevention of C. diff. infection.

“There are now a large number of products available, and they contain a large variety of strains of organisms, so this has been a difficult area to study,” he said. However, he maintains it is prudent at this point to avoid probiotics in the ICU because the risks are not confined to the patient making this choice.

“My concern is not just the lack of evidence of benefit relative to the risk for the patient but the potential for probiotics in the ICU to place other patients at risk,” Dr. Mayer said.

Others have also noted the potential benefits of probiotics in the ICU, but the promise remains elusive. In a 2018 review article published in the Journal of Emergency and Critical Care Medicine, the authors evaluated a series of potential applications of probiotics in critically ill patients. These included treatment of ventilator-associated pneumonia (VAP), catheter-associated urinary tract infections (CAUTI), and surgical-site infections (SSI). For each, the data were negative or inconclusive.

Over the 4 years that have passed since the review was published, several trials have further explored the potential benefits of probiotics in the ICU but none have changed this basic conclusion. For example, a 2021 multinational trial, published in The Lancet, randomized more than 2,600 patients to probiotics or placebo and showed no effect on VAP incidence (21.9% vs. 21.3%).

The lead author of the 2018 review, Heather A. Vitko, PhD, an associate professor in the department of acute and tertiary care, University of Pittsburgh School of Nursing, also emphasized that the potential for benefit cannot be considered without the potential for risk. She, like Dr. Mayer, cited the case studies implicating probiotics in systemic infections.

For administration, probiotic capsules or sachets “often need to be opened for administration through a feeding tube,” she noted. The risk of contamination comes from both the air and contaminated hands, the latter of which “can cause a translocation to a central line catheter where the microbes have direct entry into the systemic circulation.”

She did not call for a ban of probiotics in the ICU, but she did recommend “a precautionary approach,” encouraging clinicians to “distinguish between reality [of what has been proven] and what is presented in the marketing of antibiotics.”

Dr. Mayer and Dr. Vitko have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NASHVILLE, TENN. – Supported by several cases series, a large cohort analysis has associated exposure to probiotics in the intensive care unit with a measurable increase in bacteremia and bacteremia-related mortality due to organisms in these preparations, according to new findings presented at the annual meeting of the American College of Chest Physicians (CHEST).

According to data presented by Scott Mayer, MD, chief resident at HealthONE Denver, which is part of the HCA Healthcare chain of hospitals, the risk is increased by any probiotic exposure. However, the risk is particularly acute for powdered formulations, presumably because powder more easily disseminates to contaminate central venous catheters.

“We think that probiotics should be eliminated entirely from the ICU. If not, we encourage eliminating the powder formulations,” said Dr. Mayer, who led the study.

The data linking probiotics to ICU bacteremia were drawn from 23,533 ICU admissions over a 5-year period in the HCA hospital database. Bacteremia proven to be probiotic-related was uncommon (0.37%), but the consequences were serious.

For those with probiotic-related bacteremia, the mortality rate was 25.6% or essentially twofold greater than the 13.5% mortality rate among those without probiotic bacteremia. An odds ratio drawn from a regression analysis confirmed a significant difference (OR, 2.23; 95% confidence interval, 1.30-3.71; P < .01).

“The absolute risk of mortality is modest but not insignificant,” said Dr. Mayer. This suggests one probiotic-related mortality for about every 200 patients taking a probiotic in the ICU.

These deaths occur without any clear compensatory benefit from taking probiotics, according to Dr. Mayer. There is a long list of potential benefits from probiotics that might be relevant to patients in the ICU, particularly prophylaxis for Clostridioides difficile infection, but also including a variety of gastrointestinal disorders, such as irritable bowel syndrome; however, none of these are firmly established in general, and particularly for patients in the ICU.

“The American College of Gastroenterology currently recommends against probiotics for the prevention of C. diff.,” Dr. Mayer said. Although the American Gastroenterological Association has issued a “conditional recommendation” for prevention of C. diff. infection with probiotics, Dr. Mayer pointed out this is qualified by a “low quality of evidence” and it is not specific to the ICU setting.

“The evidence for benefit is weak or nonexistent, but the risks are real,” Dr. Mayer said.

To confirm that probiotic-associated ICU bacteremias in the HCA hospital database were, in fact, related to probiotics being taken by patients at time of admission, Dr. Mayer evaluated the record of each of the 86 patients with probiotic bacteremia–associated mortality.

“I identified the organism that grew from the blood cultures to confirm that it was contained in the probiotic the patient was taking,” explained Dr. Mayer, who said this information was available in the electronic medical records.

The risk of probiotic-associated bacteremia in ICU patients was consistent with a series of case series that prompted the study. Dr. Mayer explained that he became interested when he encountered patients on his ICU rounds who were taking probiotics. He knew very little about these agents and explored the medical literature to see what evidence was available.

“I found several case reports of ICU patients with probiotic-associated infections, several of which were suspected of being associated with contamination of the central lines,” Dr. Mayer said. In one case, the patient was not taking a probiotic, but a patient in an adjacent bed was receiving a powdered probiotic that was implicated. This prompted suspicion that the cause was central-line contamination.

This was evaluated in the HCA ICU database and also found to be a significant risk. Among the 67 patients in whom a capsule or tablet was used, the rate of probiotic-associated bacteremia was 0.33%. For those in which the probiotic was a powdered formulation, the rate was 0.76%, a significant difference (P < .01).

Dr. Mayer acknowledged that these data do not rule out all potential benefits from probiotics in the ICU. He believes an obstacle to proving benefit has been the heterogeneity of available products, which are likely to be relevant to any therapeutic role, including prevention of C. diff. infection.

“There are now a large number of products available, and they contain a large variety of strains of organisms, so this has been a difficult area to study,” he said. However, he maintains it is prudent at this point to avoid probiotics in the ICU because the risks are not confined to the patient making this choice.

“My concern is not just the lack of evidence of benefit relative to the risk for the patient but the potential for probiotics in the ICU to place other patients at risk,” Dr. Mayer said.

Others have also noted the potential benefits of probiotics in the ICU, but the promise remains elusive. In a 2018 review article published in the Journal of Emergency and Critical Care Medicine, the authors evaluated a series of potential applications of probiotics in critically ill patients. These included treatment of ventilator-associated pneumonia (VAP), catheter-associated urinary tract infections (CAUTI), and surgical-site infections (SSI). For each, the data were negative or inconclusive.

Over the 4 years that have passed since the review was published, several trials have further explored the potential benefits of probiotics in the ICU but none have changed this basic conclusion. For example, a 2021 multinational trial, published in The Lancet, randomized more than 2,600 patients to probiotics or placebo and showed no effect on VAP incidence (21.9% vs. 21.3%).

The lead author of the 2018 review, Heather A. Vitko, PhD, an associate professor in the department of acute and tertiary care, University of Pittsburgh School of Nursing, also emphasized that the potential for benefit cannot be considered without the potential for risk. She, like Dr. Mayer, cited the case studies implicating probiotics in systemic infections.

For administration, probiotic capsules or sachets “often need to be opened for administration through a feeding tube,” she noted. The risk of contamination comes from both the air and contaminated hands, the latter of which “can cause a translocation to a central line catheter where the microbes have direct entry into the systemic circulation.”

She did not call for a ban of probiotics in the ICU, but she did recommend “a precautionary approach,” encouraging clinicians to “distinguish between reality [of what has been proven] and what is presented in the marketing of antibiotics.”

Dr. Mayer and Dr. Vitko have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Results of a new study indicate that opt-out HIV testing, in particular “notional consent testing” where a patient is not asked or counseled before conducting the test, is an effective tool for identifying undiagnosed HIV cases in populations with an HIV positivity rate greater than 0.2%.

On implementation of opt-out testing of patients aged 18-59 years admitted to the ED at St. George’s University Hospital in London, the proportion of tests performed increased from 57.9% to 69%. Upon increasing the age range to those 16 and older and implementing notional consent, overall testing coverage improved to 74.2%.

“An opt-out HIV testing program in the emergency department provides an excellent opportunity to diagnose patients who do not perceive themselves to be at risk or who have never tested before,” lead author Rebecca Marchant, MBBS, of St. George’s Hospital, said in an interview.

The study was published online in HIV Medicine.

She continued, “I think this take-away message would be applicable to other countries with prevalence of HIV greater than 2 per 1,000 people, as routine HIV testing in areas of high prevalence removes the need to target testing of specific populations, potentially preventing stigmatization.”

Despite excellent uptake of HIV testing in antenatal and sexual health services, 6% of people living in the United Kingdom are unaware of their status, and up to 42% of people living with HIV are diagnosed at a late stage of infection. Because blood is routinely drawn in EDs, it’s an excellent opportunity for increased testing. Late-stage diagnosis carries an increased risk of developing an AIDS-related illness, a sevenfold increase in risk for death in the first year after diagnosis, and increased rates of HIV transmission and health care costs.

The study was conducted in a region of London that has an HIV prevalence of 5.4 cases per 1,000 residents aged 15-59 years. Opt-out HIV testing was implemented in February 2019 for people aged 18-59, and in March 2021, this was changed to include those aged 16-plus years along with a move to notional consent.

Out of 78,333 HIV tests, there were 1054 reactive results. Of these, 728 (69%) were known people living with HIV, 8 (0.8%) were not contactable, 2 (0.2%) retested elsewhere and 3 (0.3%) declined a retest. A total of 259 false positives were determined by follow-up testing.

Of those who received a confirmed HIV diagnosis, 50 (4.8%) were newly diagnosed. HIV was suspected in only 22% of these people, and 48% had never previously tested for the virus. New diagnoses were 80% male with a median age of 42 years. CD4 counts varied widely (3 cells/mcL to 1,344 cells/mcL), with 60% diagnosed at a late stage (CD4 < 350 cells/mcL) and 40% with advanced immunosuppression (CD4 < 200 cells/mcL).

“It did not surprise me that heterosexuals made up 62% of all new diagnoses,” Dr. Marchant noted. “This is because routine opt-out testing in the ED offers the opportunity to test people who don’t perceive themselves to be at risk or who have never tested before, and I believe heterosexual people are more likely to fit into those categories. In London, new HIV diagnoses amongst men who have sex with men have fallen year on year likely due to pre-exposure prophylaxis being more readily available and a generally good awareness of HIV and testing amongst MSM.”

Michael D. Levine, MD, associate professor of emergency medicine at the University of California, Los Angeles, agreed with its main findings.

“Doing widespread screening of patients in the emergency department is a feasible option,” Dr. Levine, who was not involved with this study, said in an interview. “But it only makes sense to do this in a population with some prevalence of HIV. With some forms of testing, like rapid HIV tests, you only get a presumptive positive and you then have a confirmatory test. The presumptive positives do have false positives associated with them. So if you’re in a population with very few cases of HIV, and you have a significant number of false positives, that’s going to be problematic. It’s going to add a tremendous amount of stress to the patient.”

A version of this article first appeared on Medscape.com.

Results of a new study indicate that opt-out HIV testing, in particular “notional consent testing” where a patient is not asked or counseled before conducting the test, is an effective tool for identifying undiagnosed HIV cases in populations with an HIV positivity rate greater than 0.2%.

On implementation of opt-out testing of patients aged 18-59 years admitted to the ED at St. George’s University Hospital in London, the proportion of tests performed increased from 57.9% to 69%. Upon increasing the age range to those 16 and older and implementing notional consent, overall testing coverage improved to 74.2%.

“An opt-out HIV testing program in the emergency department provides an excellent opportunity to diagnose patients who do not perceive themselves to be at risk or who have never tested before,” lead author Rebecca Marchant, MBBS, of St. George’s Hospital, said in an interview.

The study was published online in HIV Medicine.

She continued, “I think this take-away message would be applicable to other countries with prevalence of HIV greater than 2 per 1,000 people, as routine HIV testing in areas of high prevalence removes the need to target testing of specific populations, potentially preventing stigmatization.”

Despite excellent uptake of HIV testing in antenatal and sexual health services, 6% of people living in the United Kingdom are unaware of their status, and up to 42% of people living with HIV are diagnosed at a late stage of infection. Because blood is routinely drawn in EDs, it’s an excellent opportunity for increased testing. Late-stage diagnosis carries an increased risk of developing an AIDS-related illness, a sevenfold increase in risk for death in the first year after diagnosis, and increased rates of HIV transmission and health care costs.

The study was conducted in a region of London that has an HIV prevalence of 5.4 cases per 1,000 residents aged 15-59 years. Opt-out HIV testing was implemented in February 2019 for people aged 18-59, and in March 2021, this was changed to include those aged 16-plus years along with a move to notional consent.

Out of 78,333 HIV tests, there were 1054 reactive results. Of these, 728 (69%) were known people living with HIV, 8 (0.8%) were not contactable, 2 (0.2%) retested elsewhere and 3 (0.3%) declined a retest. A total of 259 false positives were determined by follow-up testing.

Of those who received a confirmed HIV diagnosis, 50 (4.8%) were newly diagnosed. HIV was suspected in only 22% of these people, and 48% had never previously tested for the virus. New diagnoses were 80% male with a median age of 42 years. CD4 counts varied widely (3 cells/mcL to 1,344 cells/mcL), with 60% diagnosed at a late stage (CD4 < 350 cells/mcL) and 40% with advanced immunosuppression (CD4 < 200 cells/mcL).

“It did not surprise me that heterosexuals made up 62% of all new diagnoses,” Dr. Marchant noted. “This is because routine opt-out testing in the ED offers the opportunity to test people who don’t perceive themselves to be at risk or who have never tested before, and I believe heterosexual people are more likely to fit into those categories. In London, new HIV diagnoses amongst men who have sex with men have fallen year on year likely due to pre-exposure prophylaxis being more readily available and a generally good awareness of HIV and testing amongst MSM.”

Michael D. Levine, MD, associate professor of emergency medicine at the University of California, Los Angeles, agreed with its main findings.

“Doing widespread screening of patients in the emergency department is a feasible option,” Dr. Levine, who was not involved with this study, said in an interview. “But it only makes sense to do this in a population with some prevalence of HIV. With some forms of testing, like rapid HIV tests, you only get a presumptive positive and you then have a confirmatory test. The presumptive positives do have false positives associated with them. So if you’re in a population with very few cases of HIV, and you have a significant number of false positives, that’s going to be problematic. It’s going to add a tremendous amount of stress to the patient.”

A version of this article first appeared on Medscape.com.

Results of a new study indicate that opt-out HIV testing, in particular “notional consent testing” where a patient is not asked or counseled before conducting the test, is an effective tool for identifying undiagnosed HIV cases in populations with an HIV positivity rate greater than 0.2%.

On implementation of opt-out testing of patients aged 18-59 years admitted to the ED at St. George’s University Hospital in London, the proportion of tests performed increased from 57.9% to 69%. Upon increasing the age range to those 16 and older and implementing notional consent, overall testing coverage improved to 74.2%.

“An opt-out HIV testing program in the emergency department provides an excellent opportunity to diagnose patients who do not perceive themselves to be at risk or who have never tested before,” lead author Rebecca Marchant, MBBS, of St. George’s Hospital, said in an interview.

The study was published online in HIV Medicine.

She continued, “I think this take-away message would be applicable to other countries with prevalence of HIV greater than 2 per 1,000 people, as routine HIV testing in areas of high prevalence removes the need to target testing of specific populations, potentially preventing stigmatization.”

Despite excellent uptake of HIV testing in antenatal and sexual health services, 6% of people living in the United Kingdom are unaware of their status, and up to 42% of people living with HIV are diagnosed at a late stage of infection. Because blood is routinely drawn in EDs, it’s an excellent opportunity for increased testing. Late-stage diagnosis carries an increased risk of developing an AIDS-related illness, a sevenfold increase in risk for death in the first year after diagnosis, and increased rates of HIV transmission and health care costs.

The study was conducted in a region of London that has an HIV prevalence of 5.4 cases per 1,000 residents aged 15-59 years. Opt-out HIV testing was implemented in February 2019 for people aged 18-59, and in March 2021, this was changed to include those aged 16-plus years along with a move to notional consent.

Out of 78,333 HIV tests, there were 1054 reactive results. Of these, 728 (69%) were known people living with HIV, 8 (0.8%) were not contactable, 2 (0.2%) retested elsewhere and 3 (0.3%) declined a retest. A total of 259 false positives were determined by follow-up testing.

Of those who received a confirmed HIV diagnosis, 50 (4.8%) were newly diagnosed. HIV was suspected in only 22% of these people, and 48% had never previously tested for the virus. New diagnoses were 80% male with a median age of 42 years. CD4 counts varied widely (3 cells/mcL to 1,344 cells/mcL), with 60% diagnosed at a late stage (CD4 < 350 cells/mcL) and 40% with advanced immunosuppression (CD4 < 200 cells/mcL).

“It did not surprise me that heterosexuals made up 62% of all new diagnoses,” Dr. Marchant noted. “This is because routine opt-out testing in the ED offers the opportunity to test people who don’t perceive themselves to be at risk or who have never tested before, and I believe heterosexual people are more likely to fit into those categories. In London, new HIV diagnoses amongst men who have sex with men have fallen year on year likely due to pre-exposure prophylaxis being more readily available and a generally good awareness of HIV and testing amongst MSM.”

Michael D. Levine, MD, associate professor of emergency medicine at the University of California, Los Angeles, agreed with its main findings.

“Doing widespread screening of patients in the emergency department is a feasible option,” Dr. Levine, who was not involved with this study, said in an interview. “But it only makes sense to do this in a population with some prevalence of HIV. With some forms of testing, like rapid HIV tests, you only get a presumptive positive and you then have a confirmatory test. The presumptive positives do have false positives associated with them. So if you’re in a population with very few cases of HIV, and you have a significant number of false positives, that’s going to be problematic. It’s going to add a tremendous amount of stress to the patient.”

A version of this article first appeared on Medscape.com.

There was a wide gap between patients’ perceptions of their diet quality and the reality in the SMARTER weight-loss trial of lifestyle changes, researchers report.

Only 28% of the participants had good agreement – defined as a difference of 6 points or less – between their perceived diet quality and its actual quality based on Healthy Eating Index–2015 (HEI) scores at the end of the 12-month intervention.

Even fewer – only 13% – had good agreement with their perceived and actual improvement in diet quality.

Jessica Cheng, PhD, Harvard School of Public Health, Boston, presented the findings in an oral session at the American Heart Association scientific sessions.

The study suggests that “patients can benefit from concrete advice on aspects of their diet that could most benefit by being changed,” Dr. Cheng said in an interview.

“But once they know what to change, they may need additional advice on how to make and sustain those changes. Providers may direct their patients to resources such as dietitians, medically tailored meals, MyPlate, healthy recipes, etc.,” she advised.

“The findings are not surprising given that dietary recalls are subject to recall bias and depend on the person’s baseline nutrition knowledge or literacy,” Deepika Laddu, PhD, who was not involved with this research, said in an interview.

Misperception of diet intake is common in individuals with overweight or obesity, and one 90-minute session with a dietitian is not enough, according to Dr. Laddu, assistant professor at the University of Illinois at Chicago.

“The Dietary Guidelines for Americans does a really nice job at presenting all of the options,” she said. However, “understanding what a healthy diet pattern is, or how to adopt it, is confusing, due to a lot of ‘noise’, that is, the mixed messaging and unproven health claims, which add to inadequacies in health or nutrition literacy.”

“It is important to recognize that changing dietary practices is behaviorally challenging and complex,” she emphasized.

People who are interested in making dietary changes need to have ongoing conversations with a qualified health care professional, which most often starts with their primary care clinician.

“Given the well-known time constraints during a typical clinical visit, beyond that initial conversation, it is absolutely critical that patients be referred to qualified healthcare professionals such as a registered dietitian, nurse practitioner, health coach/educator or diabetes educator, etc, for ongoing support.”

These providers can assess the patient’s initial diet, perceptions of a healthy diet, and diet goals, and address any gaps in health literacy, to enable the patient to develop long-lasting, realistic, and healthy eating behaviors.
 

Perceived vs. actual diet quality

Healthy eating is essential for heart and general health and longevity, but it is unclear if people who make lifestyle (diet and physical activity) changes to lose weight have an accurate perception of diet quality.

The researchers analyzed data from the SMARTER trial of 502 adults aged 35-58 living in the greater Pittsburgh area who were trying to lose weight.

Participants received a 90-minute weight loss counseling session addressing behavioral strategies and establishing dietary and physical activity goals. They all received instructions on how to monitor their diet, physical activity, and weight daily, using a smartphone app, a wristband tracker (Fitbit Charge 2), and a smart wireless scale. Half of the participants also received real-time personalized feedback on those behaviors, up to three times a day, via the study app.

The participants replied to two 24-hour dietary recall questionnaires at study entry and two questionnaires at 12 months.

Researchers analyzed data from the 116 participants who provided information about diet quality. At 1 year, they were asked to rate their diet quality, but also rate their diet quality 12 months earlier at baseline, on a scale of 0-100, where 100 is best.

The average weight loss at 12 months was similar in the groups with and without feedback from the app (roughly 3.2% of baseline weight), so the two study arms were combined. The participants had a mean age of 52 years; 80% were women and 87% were White. They had an average body mass index of 33 kg/m².

Based on the information from the food recall questionnaires, the researchers calculated the patients’ HEI scores at the start and end of the study. The HEI score is a measure of how well a person’s diet adheres to the 2015-2020 Dietary Guidelines for Americans. It is based on an adequate consumption of nine types of foods – total fruits, whole fruits, total vegetables, greens and beans, total protein foods, seafood, and plant proteins (up to 5 points each), and whole grains, dairy, and fatty acids (up to 10 points each) – and reduced consumption of four dietary components – refined grains, sodium, added sugars, and saturated fats (up to 10 points each).

The healthiest diet has an HEI score of 100, and the Healthy People 2020 goal was an HEI score of 74, Dr. Cheng noted.

At 12 months, on average, the participants rated their diet quality at 70.5 points, whereas the researchers calculated that their average HEI score was only 56.

Participants thought they had improved their diet quality by about 20 points, Dr. Cheng reported. “However, the HEI would suggest they’ve improved it by 1.5 points, which is not a lot out of 100.”

“Future studies should examine the effects of helping people close the gap between their perceptions and objective diet quality measurements,” Dr. Cheng said in a press release from the AHA.

The study was funded by the National Heart, Lung, and Blood Institute, a division of the National Institutes of Health. Dr. Cheng and Dr. Laddu reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There was a wide gap between patients’ perceptions of their diet quality and the reality in the SMARTER weight-loss trial of lifestyle changes, researchers report.

Only 28% of the participants had good agreement – defined as a difference of 6 points or less – between their perceived diet quality and its actual quality based on Healthy Eating Index–2015 (HEI) scores at the end of the 12-month intervention.

Even fewer – only 13% – had good agreement with their perceived and actual improvement in diet quality.

Jessica Cheng, PhD, Harvard School of Public Health, Boston, presented the findings in an oral session at the American Heart Association scientific sessions.

The study suggests that “patients can benefit from concrete advice on aspects of their diet that could most benefit by being changed,” Dr. Cheng said in an interview.

“But once they know what to change, they may need additional advice on how to make and sustain those changes. Providers may direct their patients to resources such as dietitians, medically tailored meals, MyPlate, healthy recipes, etc.,” she advised.

“The findings are not surprising given that dietary recalls are subject to recall bias and depend on the person’s baseline nutrition knowledge or literacy,” Deepika Laddu, PhD, who was not involved with this research, said in an interview.

Misperception of diet intake is common in individuals with overweight or obesity, and one 90-minute session with a dietitian is not enough, according to Dr. Laddu, assistant professor at the University of Illinois at Chicago.

“The Dietary Guidelines for Americans does a really nice job at presenting all of the options,” she said. However, “understanding what a healthy diet pattern is, or how to adopt it, is confusing, due to a lot of ‘noise’, that is, the mixed messaging and unproven health claims, which add to inadequacies in health or nutrition literacy.”

“It is important to recognize that changing dietary practices is behaviorally challenging and complex,” she emphasized.

People who are interested in making dietary changes need to have ongoing conversations with a qualified health care professional, which most often starts with their primary care clinician.

“Given the well-known time constraints during a typical clinical visit, beyond that initial conversation, it is absolutely critical that patients be referred to qualified healthcare professionals such as a registered dietitian, nurse practitioner, health coach/educator or diabetes educator, etc, for ongoing support.”

These providers can assess the patient’s initial diet, perceptions of a healthy diet, and diet goals, and address any gaps in health literacy, to enable the patient to develop long-lasting, realistic, and healthy eating behaviors.
 

Perceived vs. actual diet quality

Healthy eating is essential for heart and general health and longevity, but it is unclear if people who make lifestyle (diet and physical activity) changes to lose weight have an accurate perception of diet quality.

The researchers analyzed data from the SMARTER trial of 502 adults aged 35-58 living in the greater Pittsburgh area who were trying to lose weight.

Participants received a 90-minute weight loss counseling session addressing behavioral strategies and establishing dietary and physical activity goals. They all received instructions on how to monitor their diet, physical activity, and weight daily, using a smartphone app, a wristband tracker (Fitbit Charge 2), and a smart wireless scale. Half of the participants also received real-time personalized feedback on those behaviors, up to three times a day, via the study app.

The participants replied to two 24-hour dietary recall questionnaires at study entry and two questionnaires at 12 months.

Researchers analyzed data from the 116 participants who provided information about diet quality. At 1 year, they were asked to rate their diet quality, but also rate their diet quality 12 months earlier at baseline, on a scale of 0-100, where 100 is best.

The average weight loss at 12 months was similar in the groups with and without feedback from the app (roughly 3.2% of baseline weight), so the two study arms were combined. The participants had a mean age of 52 years; 80% were women and 87% were White. They had an average body mass index of 33 kg/m².

Based on the information from the food recall questionnaires, the researchers calculated the patients’ HEI scores at the start and end of the study. The HEI score is a measure of how well a person’s diet adheres to the 2015-2020 Dietary Guidelines for Americans. It is based on an adequate consumption of nine types of foods – total fruits, whole fruits, total vegetables, greens and beans, total protein foods, seafood, and plant proteins (up to 5 points each), and whole grains, dairy, and fatty acids (up to 10 points each) – and reduced consumption of four dietary components – refined grains, sodium, added sugars, and saturated fats (up to 10 points each).

The healthiest diet has an HEI score of 100, and the Healthy People 2020 goal was an HEI score of 74, Dr. Cheng noted.

At 12 months, on average, the participants rated their diet quality at 70.5 points, whereas the researchers calculated that their average HEI score was only 56.

Participants thought they had improved their diet quality by about 20 points, Dr. Cheng reported. “However, the HEI would suggest they’ve improved it by 1.5 points, which is not a lot out of 100.”

“Future studies should examine the effects of helping people close the gap between their perceptions and objective diet quality measurements,” Dr. Cheng said in a press release from the AHA.

The study was funded by the National Heart, Lung, and Blood Institute, a division of the National Institutes of Health. Dr. Cheng and Dr. Laddu reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There was a wide gap between patients’ perceptions of their diet quality and the reality in the SMARTER weight-loss trial of lifestyle changes, researchers report.

Only 28% of the participants had good agreement – defined as a difference of 6 points or less – between their perceived diet quality and its actual quality based on Healthy Eating Index–2015 (HEI) scores at the end of the 12-month intervention.

Even fewer – only 13% – had good agreement with their perceived and actual improvement in diet quality.

Jessica Cheng, PhD, Harvard School of Public Health, Boston, presented the findings in an oral session at the American Heart Association scientific sessions.

The study suggests that “patients can benefit from concrete advice on aspects of their diet that could most benefit by being changed,” Dr. Cheng said in an interview.

“But once they know what to change, they may need additional advice on how to make and sustain those changes. Providers may direct their patients to resources such as dietitians, medically tailored meals, MyPlate, healthy recipes, etc.,” she advised.

“The findings are not surprising given that dietary recalls are subject to recall bias and depend on the person’s baseline nutrition knowledge or literacy,” Deepika Laddu, PhD, who was not involved with this research, said in an interview.

Misperception of diet intake is common in individuals with overweight or obesity, and one 90-minute session with a dietitian is not enough, according to Dr. Laddu, assistant professor at the University of Illinois at Chicago.

“The Dietary Guidelines for Americans does a really nice job at presenting all of the options,” she said. However, “understanding what a healthy diet pattern is, or how to adopt it, is confusing, due to a lot of ‘noise’, that is, the mixed messaging and unproven health claims, which add to inadequacies in health or nutrition literacy.”

“It is important to recognize that changing dietary practices is behaviorally challenging and complex,” she emphasized.

People who are interested in making dietary changes need to have ongoing conversations with a qualified health care professional, which most often starts with their primary care clinician.

“Given the well-known time constraints during a typical clinical visit, beyond that initial conversation, it is absolutely critical that patients be referred to qualified healthcare professionals such as a registered dietitian, nurse practitioner, health coach/educator or diabetes educator, etc, for ongoing support.”

These providers can assess the patient’s initial diet, perceptions of a healthy diet, and diet goals, and address any gaps in health literacy, to enable the patient to develop long-lasting, realistic, and healthy eating behaviors.
 

Perceived vs. actual diet quality

Healthy eating is essential for heart and general health and longevity, but it is unclear if people who make lifestyle (diet and physical activity) changes to lose weight have an accurate perception of diet quality.

The researchers analyzed data from the SMARTER trial of 502 adults aged 35-58 living in the greater Pittsburgh area who were trying to lose weight.

Participants received a 90-minute weight loss counseling session addressing behavioral strategies and establishing dietary and physical activity goals. They all received instructions on how to monitor their diet, physical activity, and weight daily, using a smartphone app, a wristband tracker (Fitbit Charge 2), and a smart wireless scale. Half of the participants also received real-time personalized feedback on those behaviors, up to three times a day, via the study app.

The participants replied to two 24-hour dietary recall questionnaires at study entry and two questionnaires at 12 months.

Researchers analyzed data from the 116 participants who provided information about diet quality. At 1 year, they were asked to rate their diet quality, but also rate their diet quality 12 months earlier at baseline, on a scale of 0-100, where 100 is best.

The average weight loss at 12 months was similar in the groups with and without feedback from the app (roughly 3.2% of baseline weight), so the two study arms were combined. The participants had a mean age of 52 years; 80% were women and 87% were White. They had an average body mass index of 33 kg/m².

Based on the information from the food recall questionnaires, the researchers calculated the patients’ HEI scores at the start and end of the study. The HEI score is a measure of how well a person’s diet adheres to the 2015-2020 Dietary Guidelines for Americans. It is based on an adequate consumption of nine types of foods – total fruits, whole fruits, total vegetables, greens and beans, total protein foods, seafood, and plant proteins (up to 5 points each), and whole grains, dairy, and fatty acids (up to 10 points each) – and reduced consumption of four dietary components – refined grains, sodium, added sugars, and saturated fats (up to 10 points each).

The healthiest diet has an HEI score of 100, and the Healthy People 2020 goal was an HEI score of 74, Dr. Cheng noted.

At 12 months, on average, the participants rated their diet quality at 70.5 points, whereas the researchers calculated that their average HEI score was only 56.

Participants thought they had improved their diet quality by about 20 points, Dr. Cheng reported. “However, the HEI would suggest they’ve improved it by 1.5 points, which is not a lot out of 100.”

“Future studies should examine the effects of helping people close the gap between their perceptions and objective diet quality measurements,” Dr. Cheng said in a press release from the AHA.

The study was funded by the National Heart, Lung, and Blood Institute, a division of the National Institutes of Health. Dr. Cheng and Dr. Laddu reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Intermittent fasting (IF), defined as fasting for more than eight hours at a time, is a trend that is growing in popularity. Yet new research shows it may be linked to eating disorder (ED) behaviors.

Researchers from the University of Toronto analyzed data from more than 2700 adolescents and young adults from the Canadian Study of Adolescent Health Behaviors, and found that for women, IF was significantly associated with overeating, binge eating, vomiting, laxative use, and compulsive exercise.

IF in women was also associated with higher scores on the Eating Disorder Examination Questionnaire (EDE-Q), which was used to determine ED psychopathology.

Study investigator Kyle Ganson, PhD, assistant professor in the Factor-Inwentash Faculty of Social Work at the University of Toronto, said in an interview that evidence on the effectiveness of IF for weight loss and disease prevention is mixed, and that it’s important to understand the potential harms of IF – even if there are benefits for some.

“If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors, requiring health care professionals to be very aware of this contemporary and popular dietary trend, despite proponents on social media touting the effectiveness and benefits,” he said.

The study was published online in Eating Behaviors.
 

Touted for health benefits

The practice of IF has been gaining popularity partly because of reputable medical experts touting its health benefits. Johns Hopkins Medicine, for instance, cited evidence that IF boosts working memory, improves blood pressure, enhances physical performance, and prevents obesity. Yet there has been little research on its harms.

As part of the Canadian Study of Adolescent Health Behaviors, Dr. Ganson and associates analyzed data on 2,700 adolescents and young adults aged 16-30 recruited from social media ads in November and December 2021. The sample included women, men, and transgender or gender-nonconforming individuals.

Study participants answered questions about weight perception, current weight change behavior, engagement in IF, and participation in eating disorder behaviors. They were also administered the EDE-Q, which measures eating disorder psychopathology.

In total, 47% of women (n = 1,470), 38% of men (n = 1,060), and 52% transgender or gender-nonconforming individuals (n = 225) reported engaging in IF during the past year.

Dr. Ganson and associates found that, for women, IF in the past 12 months and past 30 days were significantly associated with all eating disorder behaviors, including overeating, loss of control, binge eating, vomiting, laxative use, compulsive exercise, and fasting – as well as higher overall EDE-Q global scores.

For men, IF in the past 12 months was significantly associated with compulsive exercise, and higher overall EDE-Q global scores.

The team found that for TGNC participants, IF was positively associated with higher EDE-Q global scores.

The investigators acknowledged some limitations with the study – the method of recruiting, which involved ads placed on social media, could cause selection bias. In addition to this, data collection methods relied heavily on participants’ self-reporting, which could also be susceptible to bias.

“Certainly, there needs to be more investigation on this dietary practice,” said Dr. Ganson. “If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors requiring healthcare professionals to be very aware of this contemporary and popular dietary trend – despite proponents on social media touting the effectiveness and benefits.”
 

Screening warranted

Dr. Ganson noted that additional research is needed to support the findings from his study, and to further illuminate the potential harms of IF.

Health care professionals “need to be aware of common, contemporary dietary trends that young people engage in and are commonly discussed on social media, such as IF,” he noted. In addition, he’d like to see health care professionals assess their patients for IF who are dieting and to follow-up with assessments for ED-related attitudes and behaviors.

“Additionally, there are likely bidirectional relationships between IF and ED attitudes and behaviors, so professionals should be aware the ways in which ED behaviors are masked as IF engagement,” Dr. Ganson said.
 

More research needed

Commenting on the findings, Angela Guarda, MD, professor of eating disorders at Johns Hopkins University and director of the eating disorders program at Johns Hopkins Hospital, both in Baltimore, said more research is needed on outcomes for IF.

“We lack a definitive answer. The reality is that IF may help some and harm others and is most likely not healthy for all,” she said, noting that the study results “support what many in the eating disorders field believe, namely that IF for someone who is at risk for an eating disorder is likely to be ill advised.”

She added that “continued research is needed to establish its safety, and for whom it may be a therapeutic versus an iatrogenic recommendation.”

The study was funded by the Connaught New Researcher Award. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Intermittent fasting (IF), defined as fasting for more than eight hours at a time, is a trend that is growing in popularity. Yet new research shows it may be linked to eating disorder (ED) behaviors.

Researchers from the University of Toronto analyzed data from more than 2700 adolescents and young adults from the Canadian Study of Adolescent Health Behaviors, and found that for women, IF was significantly associated with overeating, binge eating, vomiting, laxative use, and compulsive exercise.

IF in women was also associated with higher scores on the Eating Disorder Examination Questionnaire (EDE-Q), which was used to determine ED psychopathology.

Study investigator Kyle Ganson, PhD, assistant professor in the Factor-Inwentash Faculty of Social Work at the University of Toronto, said in an interview that evidence on the effectiveness of IF for weight loss and disease prevention is mixed, and that it’s important to understand the potential harms of IF – even if there are benefits for some.

“If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors, requiring health care professionals to be very aware of this contemporary and popular dietary trend, despite proponents on social media touting the effectiveness and benefits,” he said.

The study was published online in Eating Behaviors.
 

Touted for health benefits

The practice of IF has been gaining popularity partly because of reputable medical experts touting its health benefits. Johns Hopkins Medicine, for instance, cited evidence that IF boosts working memory, improves blood pressure, enhances physical performance, and prevents obesity. Yet there has been little research on its harms.

As part of the Canadian Study of Adolescent Health Behaviors, Dr. Ganson and associates analyzed data on 2,700 adolescents and young adults aged 16-30 recruited from social media ads in November and December 2021. The sample included women, men, and transgender or gender-nonconforming individuals.

Study participants answered questions about weight perception, current weight change behavior, engagement in IF, and participation in eating disorder behaviors. They were also administered the EDE-Q, which measures eating disorder psychopathology.

In total, 47% of women (n = 1,470), 38% of men (n = 1,060), and 52% transgender or gender-nonconforming individuals (n = 225) reported engaging in IF during the past year.

Dr. Ganson and associates found that, for women, IF in the past 12 months and past 30 days were significantly associated with all eating disorder behaviors, including overeating, loss of control, binge eating, vomiting, laxative use, compulsive exercise, and fasting – as well as higher overall EDE-Q global scores.

For men, IF in the past 12 months was significantly associated with compulsive exercise, and higher overall EDE-Q global scores.

The team found that for TGNC participants, IF was positively associated with higher EDE-Q global scores.

The investigators acknowledged some limitations with the study – the method of recruiting, which involved ads placed on social media, could cause selection bias. In addition to this, data collection methods relied heavily on participants’ self-reporting, which could also be susceptible to bias.

“Certainly, there needs to be more investigation on this dietary practice,” said Dr. Ganson. “If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors requiring healthcare professionals to be very aware of this contemporary and popular dietary trend – despite proponents on social media touting the effectiveness and benefits.”
 

Screening warranted

Dr. Ganson noted that additional research is needed to support the findings from his study, and to further illuminate the potential harms of IF.

Health care professionals “need to be aware of common, contemporary dietary trends that young people engage in and are commonly discussed on social media, such as IF,” he noted. In addition, he’d like to see health care professionals assess their patients for IF who are dieting and to follow-up with assessments for ED-related attitudes and behaviors.

“Additionally, there are likely bidirectional relationships between IF and ED attitudes and behaviors, so professionals should be aware the ways in which ED behaviors are masked as IF engagement,” Dr. Ganson said.
 

More research needed

Commenting on the findings, Angela Guarda, MD, professor of eating disorders at Johns Hopkins University and director of the eating disorders program at Johns Hopkins Hospital, both in Baltimore, said more research is needed on outcomes for IF.

“We lack a definitive answer. The reality is that IF may help some and harm others and is most likely not healthy for all,” she said, noting that the study results “support what many in the eating disorders field believe, namely that IF for someone who is at risk for an eating disorder is likely to be ill advised.”

She added that “continued research is needed to establish its safety, and for whom it may be a therapeutic versus an iatrogenic recommendation.”

The study was funded by the Connaught New Researcher Award. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Intermittent fasting (IF), defined as fasting for more than eight hours at a time, is a trend that is growing in popularity. Yet new research shows it may be linked to eating disorder (ED) behaviors.

Researchers from the University of Toronto analyzed data from more than 2700 adolescents and young adults from the Canadian Study of Adolescent Health Behaviors, and found that for women, IF was significantly associated with overeating, binge eating, vomiting, laxative use, and compulsive exercise.

IF in women was also associated with higher scores on the Eating Disorder Examination Questionnaire (EDE-Q), which was used to determine ED psychopathology.

Study investigator Kyle Ganson, PhD, assistant professor in the Factor-Inwentash Faculty of Social Work at the University of Toronto, said in an interview that evidence on the effectiveness of IF for weight loss and disease prevention is mixed, and that it’s important to understand the potential harms of IF – even if there are benefits for some.

“If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors, requiring health care professionals to be very aware of this contemporary and popular dietary trend, despite proponents on social media touting the effectiveness and benefits,” he said.

The study was published online in Eating Behaviors.
 

Touted for health benefits

The practice of IF has been gaining popularity partly because of reputable medical experts touting its health benefits. Johns Hopkins Medicine, for instance, cited evidence that IF boosts working memory, improves blood pressure, enhances physical performance, and prevents obesity. Yet there has been little research on its harms.

As part of the Canadian Study of Adolescent Health Behaviors, Dr. Ganson and associates analyzed data on 2,700 adolescents and young adults aged 16-30 recruited from social media ads in November and December 2021. The sample included women, men, and transgender or gender-nonconforming individuals.

Study participants answered questions about weight perception, current weight change behavior, engagement in IF, and participation in eating disorder behaviors. They were also administered the EDE-Q, which measures eating disorder psychopathology.

In total, 47% of women (n = 1,470), 38% of men (n = 1,060), and 52% transgender or gender-nonconforming individuals (n = 225) reported engaging in IF during the past year.

Dr. Ganson and associates found that, for women, IF in the past 12 months and past 30 days were significantly associated with all eating disorder behaviors, including overeating, loss of control, binge eating, vomiting, laxative use, compulsive exercise, and fasting – as well as higher overall EDE-Q global scores.

For men, IF in the past 12 months was significantly associated with compulsive exercise, and higher overall EDE-Q global scores.

The team found that for TGNC participants, IF was positively associated with higher EDE-Q global scores.

The investigators acknowledged some limitations with the study – the method of recruiting, which involved ads placed on social media, could cause selection bias. In addition to this, data collection methods relied heavily on participants’ self-reporting, which could also be susceptible to bias.

“Certainly, there needs to be more investigation on this dietary practice,” said Dr. Ganson. “If anything, this study shines light on the fact that engagement in IF may be connected with problematic ED behaviors requiring healthcare professionals to be very aware of this contemporary and popular dietary trend – despite proponents on social media touting the effectiveness and benefits.”
 

Screening warranted

Dr. Ganson noted that additional research is needed to support the findings from his study, and to further illuminate the potential harms of IF.

Health care professionals “need to be aware of common, contemporary dietary trends that young people engage in and are commonly discussed on social media, such as IF,” he noted. In addition, he’d like to see health care professionals assess their patients for IF who are dieting and to follow-up with assessments for ED-related attitudes and behaviors.

“Additionally, there are likely bidirectional relationships between IF and ED attitudes and behaviors, so professionals should be aware the ways in which ED behaviors are masked as IF engagement,” Dr. Ganson said.
 

More research needed

Commenting on the findings, Angela Guarda, MD, professor of eating disorders at Johns Hopkins University and director of the eating disorders program at Johns Hopkins Hospital, both in Baltimore, said more research is needed on outcomes for IF.

“We lack a definitive answer. The reality is that IF may help some and harm others and is most likely not healthy for all,” she said, noting that the study results “support what many in the eating disorders field believe, namely that IF for someone who is at risk for an eating disorder is likely to be ill advised.”

She added that “continued research is needed to establish its safety, and for whom it may be a therapeutic versus an iatrogenic recommendation.”

The study was funded by the Connaught New Researcher Award. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Brain indicators of motor impairment were distinct among children with autism spectrum disorder (ASD), those with developmental coordination disorder (DCD), and controls, in a new study.

Previous research suggests that individuals with ASD overlap in motor impairment with those with DCD. But these two conditions may differ significantly in some areas, as children with ASD tend to show weaker skills in social motor tasks such as imitation, wrote Emil Kilroy, PhD, of the University of Southern California, Los Angeles, and colleagues.

The neurobiological basis of autism remains unknown, despite many research efforts, in part because of the heterogeneity of the disease, said corresponding author Lisa Aziz-Zadeh, PhD, also of the University of Southern California, in an interview.

Comorbidity with other disorders is a strong contributing factor to heterogeneity, and approximately 80% of autistic individuals have motor impairments and meet criteria for a diagnosis of DCD, said Dr. Aziz-Zadeh. “Controlling for other comorbidities, such as developmental coordination disorder, when trying to understand the neural basis of autism is important, so that we can understand which neural circuits are related to [core symptoms of autism] and which ones are related to motor impairments that are comorbid with autism, but not necessarily part of the core symptomology,” she explained. “We focused on white matter pathways here because many researchers now think the underlying basis of autism, besides genetics, is brain connectivity differences.”

In their study published in Scientific Reports, the researchers reviewed data from whole-brain correlational tractography for 22 individuals with autism spectrum disorder, 16 with developmental coordination disorder, and 21 normally developing individuals, who served as the control group. The mean age of the participants was approximately 11 years; the age range was 8-17 years.

Overall, patterns of brain diffusion (movement of fluid, mainly water molecules, in the brain) were significantly different in ASD children, compared with typically developing children.

The ASD group showed significantly reduced diffusivity in the bilateral fronto-parietal cingulum and the left parolfactory cingulum. This finding reflects previous studies suggesting an association between brain patterns in the cingulum area and ASD. But the current study is “the first to identify the fronto-parietal and the parolfactory portions of the cingulum as well as the anterior caudal u-fibers as specific to core ASD symptomatology and not related to motor-related comorbidity,” the researchers wrote.

Differences in brain diffusivity were associated with worse performance on motor skills and behavioral measures for children with ASD and children with DCD, compared with controls.

Motor development was assessed using the Total Movement Assessment Battery for Children-2 (MABC-2) and the Florida Apraxia Battery modified for children (FAB-M). The MABC-2 is among the most common tools for measuring motor skills and identifying clinically relevant motor deficits in children and teens aged 3-16 years. The test includes three subtest scores (manual dexterity, gross-motor aiming and catching, and balance) and a total score. Scores are based on a child’s best performance on each component, and higher scores indicate better functioning. In the new study, The MABC-2 total scores averaged 10.57 for controls, compared with 5.76 in the ASD group, and 4.31 in the DCD group.

Children with ASD differed from the other groups in social measures. Social skills were measured using several tools, including the Social Responsivity Scale (SRS Total), which is a parent-completed survey that includes a total score designed to reflect the severity of social deficits in ASD. It is divided into five subscales for parents to assess a child’s social skill impairment: social awareness, social cognition, social communication, social motivation, and mannerisms. Scores for the SRS are calculated in T-scores, in which a score of 50 represents the mean. T-scores of 59 and below are generally not associated with ASD, and patients with these scores are considered to have low to no symptomatology. Scores on the SRS Total in the new study were 45.95, 77.45, and 55.81 for the controls, ASD group, and DCD group, respectively.
 

Results should raise awareness

“The results were largely predicted in our hypotheses – that we would find specific white matter pathways in autism that would differ from [what we saw in typically developing patients and those with DCD], and that diffusivity in ASD would be related to socioemotional differences,” Dr. Aziz-Zadeh said, in an interview.

“What was surprising was that some pathways that had previously been thought to be different in autism were also compromised in DCD, indicating that they were common to motor deficits which both groups shared, not to core autism symptomology,” she noted.

A message for clinicians from the study is that a dual diagnosis of DCD is often missing in ASD practice, said Dr. Aziz-Zadeh. “Given that approximately 80% of children with ASD have DCD, testing for DCD and addressing potential motor issues should be more common practice,” she said.

Dr. Aziz-Zadeh and colleagues are now investigating relationships between the brain, behavior, and the gut microbiome. “We think that understanding autism from a full-body perspective, examining interactions between the brain and the body, will be an important step in this field,” she emphasized.

The study was limited by several factors, including the small sample size, the use of only right-handed participants, and the use of self-reports by children and parents, the researchers noted. Additionally, they noted that white matter develops at different rates in different age groups, and future studies might consider age as a factor, as well as further behavioral assessments, they said.
 

Small sample size limits conclusions

“Understanding the neuroanatomic differences that may contribute to the core symptoms of ASD is a very important goal for the field, particularly how they relate to other comorbid symptoms and neurodevelopmental disorders,” said Michael Gandal, MD, of the department of psychiatry at the University of Pennsylvania, Philadelphia, and a member of the Lifespan Brain Institute at the Children’s Hospital of Philadelphia, in an interview.

“While this study provides some clues into how structural connectivity may relate to motor coordination in ASD, it will be important to replicate these findings in a much larger sample before we can really appreciate how robust these findings are and how well they generalize to the broader ASD population,” Dr. Gandal emphasized.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Gandal had no financial conflicts to disclose.

Brain indicators of motor impairment were distinct among children with autism spectrum disorder (ASD), those with developmental coordination disorder (DCD), and controls, in a new study.

Previous research suggests that individuals with ASD overlap in motor impairment with those with DCD. But these two conditions may differ significantly in some areas, as children with ASD tend to show weaker skills in social motor tasks such as imitation, wrote Emil Kilroy, PhD, of the University of Southern California, Los Angeles, and colleagues.

The neurobiological basis of autism remains unknown, despite many research efforts, in part because of the heterogeneity of the disease, said corresponding author Lisa Aziz-Zadeh, PhD, also of the University of Southern California, in an interview.

Comorbidity with other disorders is a strong contributing factor to heterogeneity, and approximately 80% of autistic individuals have motor impairments and meet criteria for a diagnosis of DCD, said Dr. Aziz-Zadeh. “Controlling for other comorbidities, such as developmental coordination disorder, when trying to understand the neural basis of autism is important, so that we can understand which neural circuits are related to [core symptoms of autism] and which ones are related to motor impairments that are comorbid with autism, but not necessarily part of the core symptomology,” she explained. “We focused on white matter pathways here because many researchers now think the underlying basis of autism, besides genetics, is brain connectivity differences.”

In their study published in Scientific Reports, the researchers reviewed data from whole-brain correlational tractography for 22 individuals with autism spectrum disorder, 16 with developmental coordination disorder, and 21 normally developing individuals, who served as the control group. The mean age of the participants was approximately 11 years; the age range was 8-17 years.

Overall, patterns of brain diffusion (movement of fluid, mainly water molecules, in the brain) were significantly different in ASD children, compared with typically developing children.

The ASD group showed significantly reduced diffusivity in the bilateral fronto-parietal cingulum and the left parolfactory cingulum. This finding reflects previous studies suggesting an association between brain patterns in the cingulum area and ASD. But the current study is “the first to identify the fronto-parietal and the parolfactory portions of the cingulum as well as the anterior caudal u-fibers as specific to core ASD symptomatology and not related to motor-related comorbidity,” the researchers wrote.

Differences in brain diffusivity were associated with worse performance on motor skills and behavioral measures for children with ASD and children with DCD, compared with controls.

Motor development was assessed using the Total Movement Assessment Battery for Children-2 (MABC-2) and the Florida Apraxia Battery modified for children (FAB-M). The MABC-2 is among the most common tools for measuring motor skills and identifying clinically relevant motor deficits in children and teens aged 3-16 years. The test includes three subtest scores (manual dexterity, gross-motor aiming and catching, and balance) and a total score. Scores are based on a child’s best performance on each component, and higher scores indicate better functioning. In the new study, The MABC-2 total scores averaged 10.57 for controls, compared with 5.76 in the ASD group, and 4.31 in the DCD group.

Children with ASD differed from the other groups in social measures. Social skills were measured using several tools, including the Social Responsivity Scale (SRS Total), which is a parent-completed survey that includes a total score designed to reflect the severity of social deficits in ASD. It is divided into five subscales for parents to assess a child’s social skill impairment: social awareness, social cognition, social communication, social motivation, and mannerisms. Scores for the SRS are calculated in T-scores, in which a score of 50 represents the mean. T-scores of 59 and below are generally not associated with ASD, and patients with these scores are considered to have low to no symptomatology. Scores on the SRS Total in the new study were 45.95, 77.45, and 55.81 for the controls, ASD group, and DCD group, respectively.
 

Results should raise awareness

“The results were largely predicted in our hypotheses – that we would find specific white matter pathways in autism that would differ from [what we saw in typically developing patients and those with DCD], and that diffusivity in ASD would be related to socioemotional differences,” Dr. Aziz-Zadeh said, in an interview.

“What was surprising was that some pathways that had previously been thought to be different in autism were also compromised in DCD, indicating that they were common to motor deficits which both groups shared, not to core autism symptomology,” she noted.

A message for clinicians from the study is that a dual diagnosis of DCD is often missing in ASD practice, said Dr. Aziz-Zadeh. “Given that approximately 80% of children with ASD have DCD, testing for DCD and addressing potential motor issues should be more common practice,” she said.

Dr. Aziz-Zadeh and colleagues are now investigating relationships between the brain, behavior, and the gut microbiome. “We think that understanding autism from a full-body perspective, examining interactions between the brain and the body, will be an important step in this field,” she emphasized.

The study was limited by several factors, including the small sample size, the use of only right-handed participants, and the use of self-reports by children and parents, the researchers noted. Additionally, they noted that white matter develops at different rates in different age groups, and future studies might consider age as a factor, as well as further behavioral assessments, they said.
 

Small sample size limits conclusions

“Understanding the neuroanatomic differences that may contribute to the core symptoms of ASD is a very important goal for the field, particularly how they relate to other comorbid symptoms and neurodevelopmental disorders,” said Michael Gandal, MD, of the department of psychiatry at the University of Pennsylvania, Philadelphia, and a member of the Lifespan Brain Institute at the Children’s Hospital of Philadelphia, in an interview.

“While this study provides some clues into how structural connectivity may relate to motor coordination in ASD, it will be important to replicate these findings in a much larger sample before we can really appreciate how robust these findings are and how well they generalize to the broader ASD population,” Dr. Gandal emphasized.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Gandal had no financial conflicts to disclose.

Brain indicators of motor impairment were distinct among children with autism spectrum disorder (ASD), those with developmental coordination disorder (DCD), and controls, in a new study.

Previous research suggests that individuals with ASD overlap in motor impairment with those with DCD. But these two conditions may differ significantly in some areas, as children with ASD tend to show weaker skills in social motor tasks such as imitation, wrote Emil Kilroy, PhD, of the University of Southern California, Los Angeles, and colleagues.

The neurobiological basis of autism remains unknown, despite many research efforts, in part because of the heterogeneity of the disease, said corresponding author Lisa Aziz-Zadeh, PhD, also of the University of Southern California, in an interview.

Comorbidity with other disorders is a strong contributing factor to heterogeneity, and approximately 80% of autistic individuals have motor impairments and meet criteria for a diagnosis of DCD, said Dr. Aziz-Zadeh. “Controlling for other comorbidities, such as developmental coordination disorder, when trying to understand the neural basis of autism is important, so that we can understand which neural circuits are related to [core symptoms of autism] and which ones are related to motor impairments that are comorbid with autism, but not necessarily part of the core symptomology,” she explained. “We focused on white matter pathways here because many researchers now think the underlying basis of autism, besides genetics, is brain connectivity differences.”

In their study published in Scientific Reports, the researchers reviewed data from whole-brain correlational tractography for 22 individuals with autism spectrum disorder, 16 with developmental coordination disorder, and 21 normally developing individuals, who served as the control group. The mean age of the participants was approximately 11 years; the age range was 8-17 years.

Overall, patterns of brain diffusion (movement of fluid, mainly water molecules, in the brain) were significantly different in ASD children, compared with typically developing children.

The ASD group showed significantly reduced diffusivity in the bilateral fronto-parietal cingulum and the left parolfactory cingulum. This finding reflects previous studies suggesting an association between brain patterns in the cingulum area and ASD. But the current study is “the first to identify the fronto-parietal and the parolfactory portions of the cingulum as well as the anterior caudal u-fibers as specific to core ASD symptomatology and not related to motor-related comorbidity,” the researchers wrote.

Differences in brain diffusivity were associated with worse performance on motor skills and behavioral measures for children with ASD and children with DCD, compared with controls.

Motor development was assessed using the Total Movement Assessment Battery for Children-2 (MABC-2) and the Florida Apraxia Battery modified for children (FAB-M). The MABC-2 is among the most common tools for measuring motor skills and identifying clinically relevant motor deficits in children and teens aged 3-16 years. The test includes three subtest scores (manual dexterity, gross-motor aiming and catching, and balance) and a total score. Scores are based on a child’s best performance on each component, and higher scores indicate better functioning. In the new study, The MABC-2 total scores averaged 10.57 for controls, compared with 5.76 in the ASD group, and 4.31 in the DCD group.

Children with ASD differed from the other groups in social measures. Social skills were measured using several tools, including the Social Responsivity Scale (SRS Total), which is a parent-completed survey that includes a total score designed to reflect the severity of social deficits in ASD. It is divided into five subscales for parents to assess a child’s social skill impairment: social awareness, social cognition, social communication, social motivation, and mannerisms. Scores for the SRS are calculated in T-scores, in which a score of 50 represents the mean. T-scores of 59 and below are generally not associated with ASD, and patients with these scores are considered to have low to no symptomatology. Scores on the SRS Total in the new study were 45.95, 77.45, and 55.81 for the controls, ASD group, and DCD group, respectively.
 

Results should raise awareness

“The results were largely predicted in our hypotheses – that we would find specific white matter pathways in autism that would differ from [what we saw in typically developing patients and those with DCD], and that diffusivity in ASD would be related to socioemotional differences,” Dr. Aziz-Zadeh said, in an interview.

“What was surprising was that some pathways that had previously been thought to be different in autism were also compromised in DCD, indicating that they were common to motor deficits which both groups shared, not to core autism symptomology,” she noted.

A message for clinicians from the study is that a dual diagnosis of DCD is often missing in ASD practice, said Dr. Aziz-Zadeh. “Given that approximately 80% of children with ASD have DCD, testing for DCD and addressing potential motor issues should be more common practice,” she said.

Dr. Aziz-Zadeh and colleagues are now investigating relationships between the brain, behavior, and the gut microbiome. “We think that understanding autism from a full-body perspective, examining interactions between the brain and the body, will be an important step in this field,” she emphasized.

The study was limited by several factors, including the small sample size, the use of only right-handed participants, and the use of self-reports by children and parents, the researchers noted. Additionally, they noted that white matter develops at different rates in different age groups, and future studies might consider age as a factor, as well as further behavioral assessments, they said.
 

Small sample size limits conclusions

“Understanding the neuroanatomic differences that may contribute to the core symptoms of ASD is a very important goal for the field, particularly how they relate to other comorbid symptoms and neurodevelopmental disorders,” said Michael Gandal, MD, of the department of psychiatry at the University of Pennsylvania, Philadelphia, and a member of the Lifespan Brain Institute at the Children’s Hospital of Philadelphia, in an interview.

“While this study provides some clues into how structural connectivity may relate to motor coordination in ASD, it will be important to replicate these findings in a much larger sample before we can really appreciate how robust these findings are and how well they generalize to the broader ASD population,” Dr. Gandal emphasized.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Gandal had no financial conflicts to disclose.

The asthma medication tezepelumab, added to subcutaneous immunotherapy treatment (SCIT), may provide better, longer-lasting symptom relief than allergy shots alone for patients with allergic rhinitis caused by cat allergens, according to results of a phase 1/2 clinical trial.

“One year of allergen immunotherapy [AIT] combined with tezepelumab was significantly more effective than SCIT alone in reducing the nasal response to allergen challenge both at the end of treatment and one year after stopping treatment,” lead study author Jonathan Corren, MD, of the University of California, Los Angeles, and his colleagues wrote in The Journal of Allergy and Clinical Immunology.

“This persistent improvement in clinical response was paralleled by reductions in nasal transcripts for multiple immunologic pathways, including mast cell activation.”

The study was cited in a news release from the National Institutes of Health that said that the approach may work in a similar way with other allergens.

The Food and Drug Administration recently approved tezepelumab for the treatment of severe asthma in people aged 12 years and older. Tezelumab, a monoclonal antibody, works by blocking the cytokine thymic stromal lymphopoietin (TSLP).

“Cells that cover the surface of organs like the skin and intestines or that line the inside of the nose and lungs rapidly secrete TSLP in response to signals of potential danger,” according to the NIH news release. “In allergic disease, TSLP helps initiate an overreactive immune response to otherwise harmless substances like cat dander, provoking airway inflammation that leads to the symptoms of allergic rhinitis.”
 

Testing an enhanced strategy

The double-blind CATNIP trial was conducted by Dr. Corren and colleagues at nine sites in the United States. The trial included patients aged 18-65 years who’d had moderate to severe cat-induced allergic rhinitis for at least 2 years from 2015 to 2019.

The researchers excluded patients with recurrent acute or chronic sinusitis. They excluded patients who had undergone SCIT with cat allergen within the past 10 years or seasonal or perennial allergen sensitivity during nasal challenges. They also excluded persons with a history of persistent asthma.

In the parallel-design study, 121 participants were randomly allocated into four groups: 32 patients were treated with intravenous tezepelumab plus cat SCIT, 31 received the allergy shots alone, 30 received tezepelumab alone, and 28 received placebo alone for 52 weeks, followed by 52 weeks of observation.

Participants received SCIT (10,000 bioequivalent allergy units per milliliter) or matched placebo via subcutaneous injections weekly in increasing doses for around 12 weeks, followed by monthly maintenance injections (4,000 BAU or maximum tolerated dose) until week 48.

They received tezepelumab (700 mg IV) or matched placebo 1-3 days prior to the SCIT or placebo SCIT injections once every 4 weeks through week 24, then before or on the same day as the SCIT or placebo injections through week 48.
 

Measures of effectiveness

Participants were also given nasal allergy challenges – one spritz of a nasal spray containing cat allergen extract in each nostril at screening, baseline, and weeks 26, 52, 78, and 104. The researchers recorded participants’ total nasal symptom score (TNSS) and peak nasal inspiratory flow at 5, 15, 30, and 60 minutes after being sprayed and hourly for up to 6 hours post challenge. Blood and nasal cell samples were also collected.

The research team performed skin prick tests using serial dilutions of cat extract and an intradermal skin test (IDST) using the concentration of allergen that produced an early response of at least 15 mm at baseline. They measured early-phase responses for the both tests at 15 minutes and late-phase response to the IDST at 6 hours.

They measured serum levels of cat dander–specific IgE, IgG4, and total IgE using fluoroenzyme immunoassay. They measured serum interleukin-5 and IL-13 using high-sensitivity single-molecule digital immunoassay and performed nasal brushing using a 3-mm cytology brush 6 hours after a nasal allergy challenge. They performed whole-genome transcriptional profiling on the extracted RNA.
 

Combination therapy worked better and longer

The combined therapy worked better while being administered. Although the allergy shots alone stopped working after they were discontinued, the combination continued to benefit participants 1 year after that therapy ended.

At week 52, statistically significant reductions in TNSS induced by nasal allergy challenges occurred in patients receiving tezepelumab plus SCIT compared with patients receiving SCIT alone.

At week 104, 1 year after treatment ended, the primary endpoint TNSS was not significantly different in the tezepelumab-plus-SCIT group than in the SCIT-alone group, but TNSS peak 0–1 hour was significantly lower in the combination treatment group than in the SCIT-alone group.

In analysis of gene expression from nasal epithelial samples, participants who had been treated with the combination but not with either therapy by itself showed persistent modulation of the nasal immunologic environment, including diminished mast cell function. This was explained in large part by decreased transcription of the gene TPSAB1 (tryptase). Tryptase protein in nasal fluid was also decreased in the combination group, compared with the SCIT-alone group.

Adverse and serious adverse events, including infections and infestations as well as respiratory, thoracic, mediastinal, gastrointestinal, immune system, and nervous system disorders, did not differ significantly between treatment groups.
 

Four independent experts welcome the results

Patricia Lynne Lugar, MD, associate professor of medicine in the division of pulmonology, allergy, and critical care medicine at Duke University, Durham, N.C., found the results, especially the 1-year posttreatment response durability, surprising.

“AIT is a very effective treatment that often provides prolonged symptom improvement and is ‘curative’ in many cases,” she said in an interview. “If further studies show that tezepelumab offers long-term results, more patients might opt for combination therapy.

“A significant strength of the study is its evaluation of responses of the combination therapy on cellular output and gene expression,” Dr. Lugar added. “The mechanism by which AIT modulates the allergic response is largely understood. Tezepelumab may augment this modulation to alter the Th2 response upon exposure to the allergens.”
 

Will payors cover the prohibitively costly biologic?

Scott Frank, MD, associate professor in the department of family medicine and community health at Case Western Reserve University, Cleveland, called the study well designed and rigorous.

“The practicality of the approach may be limited by the need for intravenous administration of tezepelumab in addition to the traditional allergy shot,” he noted by email, “and the cost of this therapeutic approach is not addressed.”

Christopher Brooks, MD, clinical assistant professor of allergy and immunology in the department of otolaryngology at Ohio State University Wexner Medical Center, Columbus, also pointed out the drug’s cost.

“Tezepelumab is currently an expensive biologic, so it remains to be seen whether patients and payors will be willing to pay for this add-on medication when AIT by itself still remains very effective,” he said by email.

“AIT is most effective when given for 5 years, so it also remains to be seen whether the results and conclusions of this study would still hold true if done for the typical 5-year treatment period,” he added.

Stokes Peebles, MD, professor of medicine in the division of allergy, pulmonary, and critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., called the study “very well designed by a highly respected group of investigators using well-matched study populations.

“Tezepelumab has been shown to work in asthma, and there is no reason to think it would not work in allergic rhinitis,” he said in an interview.

“However, while the results of the combined therapy were statistically significant, their clinical significance was not clear. Patients do not care about statistical significance. They want to know whether a drug will be clinically significant,” he added.

Many people avoid cat allergy symptoms by avoiding cats and, in some cases, by avoiding people who live with cats, he said. Medical therapy, usually involving nasal corticosteroids and antihistamines, helps most people avoid cat allergy symptoms.

“Patients with bad allergies who have not done well with SCIT may consider adding tezepelumab, but it incurs a major cost. If medical therapy doesn’t work, allergy shots are available at roughly $3,000 per year. Adding tezepelumab costs around $40,000 more per year,” he explained. “Does the slight clinical benefit justify the greatly increased cost?”

The authors and uninvolved experts recommend further related research.

The research was supported by the National Institute of Allergy and Infectious Diseases. AstraZeneca and Amgen donated the drug used in the study. Dr. Corren reported financial relationships with AstraZeneca, and one coauthor reported relevant financial relationships with Amgen and other pharmaceutical companies. The remaining coauthors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The asthma medication tezepelumab, added to subcutaneous immunotherapy treatment (SCIT), may provide better, longer-lasting symptom relief than allergy shots alone for patients with allergic rhinitis caused by cat allergens, according to results of a phase 1/2 clinical trial.

“One year of allergen immunotherapy [AIT] combined with tezepelumab was significantly more effective than SCIT alone in reducing the nasal response to allergen challenge both at the end of treatment and one year after stopping treatment,” lead study author Jonathan Corren, MD, of the University of California, Los Angeles, and his colleagues wrote in The Journal of Allergy and Clinical Immunology.

“This persistent improvement in clinical response was paralleled by reductions in nasal transcripts for multiple immunologic pathways, including mast cell activation.”

The study was cited in a news release from the National Institutes of Health that said that the approach may work in a similar way with other allergens.

The Food and Drug Administration recently approved tezepelumab for the treatment of severe asthma in people aged 12 years and older. Tezelumab, a monoclonal antibody, works by blocking the cytokine thymic stromal lymphopoietin (TSLP).

“Cells that cover the surface of organs like the skin and intestines or that line the inside of the nose and lungs rapidly secrete TSLP in response to signals of potential danger,” according to the NIH news release. “In allergic disease, TSLP helps initiate an overreactive immune response to otherwise harmless substances like cat dander, provoking airway inflammation that leads to the symptoms of allergic rhinitis.”
 

Testing an enhanced strategy

The double-blind CATNIP trial was conducted by Dr. Corren and colleagues at nine sites in the United States. The trial included patients aged 18-65 years who’d had moderate to severe cat-induced allergic rhinitis for at least 2 years from 2015 to 2019.

The researchers excluded patients with recurrent acute or chronic sinusitis. They excluded patients who had undergone SCIT with cat allergen within the past 10 years or seasonal or perennial allergen sensitivity during nasal challenges. They also excluded persons with a history of persistent asthma.

In the parallel-design study, 121 participants were randomly allocated into four groups: 32 patients were treated with intravenous tezepelumab plus cat SCIT, 31 received the allergy shots alone, 30 received tezepelumab alone, and 28 received placebo alone for 52 weeks, followed by 52 weeks of observation.

Participants received SCIT (10,000 bioequivalent allergy units per milliliter) or matched placebo via subcutaneous injections weekly in increasing doses for around 12 weeks, followed by monthly maintenance injections (4,000 BAU or maximum tolerated dose) until week 48.

They received tezepelumab (700 mg IV) or matched placebo 1-3 days prior to the SCIT or placebo SCIT injections once every 4 weeks through week 24, then before or on the same day as the SCIT or placebo injections through week 48.
 

Measures of effectiveness

Participants were also given nasal allergy challenges – one spritz of a nasal spray containing cat allergen extract in each nostril at screening, baseline, and weeks 26, 52, 78, and 104. The researchers recorded participants’ total nasal symptom score (TNSS) and peak nasal inspiratory flow at 5, 15, 30, and 60 minutes after being sprayed and hourly for up to 6 hours post challenge. Blood and nasal cell samples were also collected.

The research team performed skin prick tests using serial dilutions of cat extract and an intradermal skin test (IDST) using the concentration of allergen that produced an early response of at least 15 mm at baseline. They measured early-phase responses for the both tests at 15 minutes and late-phase response to the IDST at 6 hours.

They measured serum levels of cat dander–specific IgE, IgG4, and total IgE using fluoroenzyme immunoassay. They measured serum interleukin-5 and IL-13 using high-sensitivity single-molecule digital immunoassay and performed nasal brushing using a 3-mm cytology brush 6 hours after a nasal allergy challenge. They performed whole-genome transcriptional profiling on the extracted RNA.
 

Combination therapy worked better and longer

The combined therapy worked better while being administered. Although the allergy shots alone stopped working after they were discontinued, the combination continued to benefit participants 1 year after that therapy ended.

At week 52, statistically significant reductions in TNSS induced by nasal allergy challenges occurred in patients receiving tezepelumab plus SCIT compared with patients receiving SCIT alone.

At week 104, 1 year after treatment ended, the primary endpoint TNSS was not significantly different in the tezepelumab-plus-SCIT group than in the SCIT-alone group, but TNSS peak 0–1 hour was significantly lower in the combination treatment group than in the SCIT-alone group.

In analysis of gene expression from nasal epithelial samples, participants who had been treated with the combination but not with either therapy by itself showed persistent modulation of the nasal immunologic environment, including diminished mast cell function. This was explained in large part by decreased transcription of the gene TPSAB1 (tryptase). Tryptase protein in nasal fluid was also decreased in the combination group, compared with the SCIT-alone group.

Adverse and serious adverse events, including infections and infestations as well as respiratory, thoracic, mediastinal, gastrointestinal, immune system, and nervous system disorders, did not differ significantly between treatment groups.
 

Four independent experts welcome the results

Patricia Lynne Lugar, MD, associate professor of medicine in the division of pulmonology, allergy, and critical care medicine at Duke University, Durham, N.C., found the results, especially the 1-year posttreatment response durability, surprising.

“AIT is a very effective treatment that often provides prolonged symptom improvement and is ‘curative’ in many cases,” she said in an interview. “If further studies show that tezepelumab offers long-term results, more patients might opt for combination therapy.

“A significant strength of the study is its evaluation of responses of the combination therapy on cellular output and gene expression,” Dr. Lugar added. “The mechanism by which AIT modulates the allergic response is largely understood. Tezepelumab may augment this modulation to alter the Th2 response upon exposure to the allergens.”
 

Will payors cover the prohibitively costly biologic?

Scott Frank, MD, associate professor in the department of family medicine and community health at Case Western Reserve University, Cleveland, called the study well designed and rigorous.

“The practicality of the approach may be limited by the need for intravenous administration of tezepelumab in addition to the traditional allergy shot,” he noted by email, “and the cost of this therapeutic approach is not addressed.”

Christopher Brooks, MD, clinical assistant professor of allergy and immunology in the department of otolaryngology at Ohio State University Wexner Medical Center, Columbus, also pointed out the drug’s cost.

“Tezepelumab is currently an expensive biologic, so it remains to be seen whether patients and payors will be willing to pay for this add-on medication when AIT by itself still remains very effective,” he said by email.

“AIT is most effective when given for 5 years, so it also remains to be seen whether the results and conclusions of this study would still hold true if done for the typical 5-year treatment period,” he added.

Stokes Peebles, MD, professor of medicine in the division of allergy, pulmonary, and critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., called the study “very well designed by a highly respected group of investigators using well-matched study populations.

“Tezepelumab has been shown to work in asthma, and there is no reason to think it would not work in allergic rhinitis,” he said in an interview.

“However, while the results of the combined therapy were statistically significant, their clinical significance was not clear. Patients do not care about statistical significance. They want to know whether a drug will be clinically significant,” he added.

Many people avoid cat allergy symptoms by avoiding cats and, in some cases, by avoiding people who live with cats, he said. Medical therapy, usually involving nasal corticosteroids and antihistamines, helps most people avoid cat allergy symptoms.

“Patients with bad allergies who have not done well with SCIT may consider adding tezepelumab, but it incurs a major cost. If medical therapy doesn’t work, allergy shots are available at roughly $3,000 per year. Adding tezepelumab costs around $40,000 more per year,” he explained. “Does the slight clinical benefit justify the greatly increased cost?”

The authors and uninvolved experts recommend further related research.

The research was supported by the National Institute of Allergy and Infectious Diseases. AstraZeneca and Amgen donated the drug used in the study. Dr. Corren reported financial relationships with AstraZeneca, and one coauthor reported relevant financial relationships with Amgen and other pharmaceutical companies. The remaining coauthors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The asthma medication tezepelumab, added to subcutaneous immunotherapy treatment (SCIT), may provide better, longer-lasting symptom relief than allergy shots alone for patients with allergic rhinitis caused by cat allergens, according to results of a phase 1/2 clinical trial.

“One year of allergen immunotherapy [AIT] combined with tezepelumab was significantly more effective than SCIT alone in reducing the nasal response to allergen challenge both at the end of treatment and one year after stopping treatment,” lead study author Jonathan Corren, MD, of the University of California, Los Angeles, and his colleagues wrote in The Journal of Allergy and Clinical Immunology.

“This persistent improvement in clinical response was paralleled by reductions in nasal transcripts for multiple immunologic pathways, including mast cell activation.”

The study was cited in a news release from the National Institutes of Health that said that the approach may work in a similar way with other allergens.

The Food and Drug Administration recently approved tezepelumab for the treatment of severe asthma in people aged 12 years and older. Tezelumab, a monoclonal antibody, works by blocking the cytokine thymic stromal lymphopoietin (TSLP).

“Cells that cover the surface of organs like the skin and intestines or that line the inside of the nose and lungs rapidly secrete TSLP in response to signals of potential danger,” according to the NIH news release. “In allergic disease, TSLP helps initiate an overreactive immune response to otherwise harmless substances like cat dander, provoking airway inflammation that leads to the symptoms of allergic rhinitis.”
 

Testing an enhanced strategy

The double-blind CATNIP trial was conducted by Dr. Corren and colleagues at nine sites in the United States. The trial included patients aged 18-65 years who’d had moderate to severe cat-induced allergic rhinitis for at least 2 years from 2015 to 2019.

The researchers excluded patients with recurrent acute or chronic sinusitis. They excluded patients who had undergone SCIT with cat allergen within the past 10 years or seasonal or perennial allergen sensitivity during nasal challenges. They also excluded persons with a history of persistent asthma.

In the parallel-design study, 121 participants were randomly allocated into four groups: 32 patients were treated with intravenous tezepelumab plus cat SCIT, 31 received the allergy shots alone, 30 received tezepelumab alone, and 28 received placebo alone for 52 weeks, followed by 52 weeks of observation.

Participants received SCIT (10,000 bioequivalent allergy units per milliliter) or matched placebo via subcutaneous injections weekly in increasing doses for around 12 weeks, followed by monthly maintenance injections (4,000 BAU or maximum tolerated dose) until week 48.

They received tezepelumab (700 mg IV) or matched placebo 1-3 days prior to the SCIT or placebo SCIT injections once every 4 weeks through week 24, then before or on the same day as the SCIT or placebo injections through week 48.
 

Measures of effectiveness

Participants were also given nasal allergy challenges – one spritz of a nasal spray containing cat allergen extract in each nostril at screening, baseline, and weeks 26, 52, 78, and 104. The researchers recorded participants’ total nasal symptom score (TNSS) and peak nasal inspiratory flow at 5, 15, 30, and 60 minutes after being sprayed and hourly for up to 6 hours post challenge. Blood and nasal cell samples were also collected.

The research team performed skin prick tests using serial dilutions of cat extract and an intradermal skin test (IDST) using the concentration of allergen that produced an early response of at least 15 mm at baseline. They measured early-phase responses for the both tests at 15 minutes and late-phase response to the IDST at 6 hours.

They measured serum levels of cat dander–specific IgE, IgG4, and total IgE using fluoroenzyme immunoassay. They measured serum interleukin-5 and IL-13 using high-sensitivity single-molecule digital immunoassay and performed nasal brushing using a 3-mm cytology brush 6 hours after a nasal allergy challenge. They performed whole-genome transcriptional profiling on the extracted RNA.
 

Combination therapy worked better and longer

The combined therapy worked better while being administered. Although the allergy shots alone stopped working after they were discontinued, the combination continued to benefit participants 1 year after that therapy ended.

At week 52, statistically significant reductions in TNSS induced by nasal allergy challenges occurred in patients receiving tezepelumab plus SCIT compared with patients receiving SCIT alone.

At week 104, 1 year after treatment ended, the primary endpoint TNSS was not significantly different in the tezepelumab-plus-SCIT group than in the SCIT-alone group, but TNSS peak 0–1 hour was significantly lower in the combination treatment group than in the SCIT-alone group.

In analysis of gene expression from nasal epithelial samples, participants who had been treated with the combination but not with either therapy by itself showed persistent modulation of the nasal immunologic environment, including diminished mast cell function. This was explained in large part by decreased transcription of the gene TPSAB1 (tryptase). Tryptase protein in nasal fluid was also decreased in the combination group, compared with the SCIT-alone group.

Adverse and serious adverse events, including infections and infestations as well as respiratory, thoracic, mediastinal, gastrointestinal, immune system, and nervous system disorders, did not differ significantly between treatment groups.
 

Four independent experts welcome the results

Patricia Lynne Lugar, MD, associate professor of medicine in the division of pulmonology, allergy, and critical care medicine at Duke University, Durham, N.C., found the results, especially the 1-year posttreatment response durability, surprising.

“AIT is a very effective treatment that often provides prolonged symptom improvement and is ‘curative’ in many cases,” she said in an interview. “If further studies show that tezepelumab offers long-term results, more patients might opt for combination therapy.

“A significant strength of the study is its evaluation of responses of the combination therapy on cellular output and gene expression,” Dr. Lugar added. “The mechanism by which AIT modulates the allergic response is largely understood. Tezepelumab may augment this modulation to alter the Th2 response upon exposure to the allergens.”
 

Will payors cover the prohibitively costly biologic?

Scott Frank, MD, associate professor in the department of family medicine and community health at Case Western Reserve University, Cleveland, called the study well designed and rigorous.

“The practicality of the approach may be limited by the need for intravenous administration of tezepelumab in addition to the traditional allergy shot,” he noted by email, “and the cost of this therapeutic approach is not addressed.”

Christopher Brooks, MD, clinical assistant professor of allergy and immunology in the department of otolaryngology at Ohio State University Wexner Medical Center, Columbus, also pointed out the drug’s cost.

“Tezepelumab is currently an expensive biologic, so it remains to be seen whether patients and payors will be willing to pay for this add-on medication when AIT by itself still remains very effective,” he said by email.

“AIT is most effective when given for 5 years, so it also remains to be seen whether the results and conclusions of this study would still hold true if done for the typical 5-year treatment period,” he added.

Stokes Peebles, MD, professor of medicine in the division of allergy, pulmonary, and critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., called the study “very well designed by a highly respected group of investigators using well-matched study populations.

“Tezepelumab has been shown to work in asthma, and there is no reason to think it would not work in allergic rhinitis,” he said in an interview.

“However, while the results of the combined therapy were statistically significant, their clinical significance was not clear. Patients do not care about statistical significance. They want to know whether a drug will be clinically significant,” he added.

Many people avoid cat allergy symptoms by avoiding cats and, in some cases, by avoiding people who live with cats, he said. Medical therapy, usually involving nasal corticosteroids and antihistamines, helps most people avoid cat allergy symptoms.

“Patients with bad allergies who have not done well with SCIT may consider adding tezepelumab, but it incurs a major cost. If medical therapy doesn’t work, allergy shots are available at roughly $3,000 per year. Adding tezepelumab costs around $40,000 more per year,” he explained. “Does the slight clinical benefit justify the greatly increased cost?”

The authors and uninvolved experts recommend further related research.

The research was supported by the National Institute of Allergy and Infectious Diseases. AstraZeneca and Amgen donated the drug used in the study. Dr. Corren reported financial relationships with AstraZeneca, and one coauthor reported relevant financial relationships with Amgen and other pharmaceutical companies. The remaining coauthors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Extreme hot or cold temperatures shifts may trigger a rise in hate speech on social media, according to researchers from the Potsdam Institute for Climate Impact Research.

What to know

• Analyzing over four billion tweets posted on the social media platform Twitter in the United States, researchers found that hate speech increased across climate zones, income groups, and belief systems when temperatures were too hot or too cold outside.
• The minimum number of hate tweets appears to occur when temperatures are between 15° and 18° C (59° to 65° F). The precise feel-good temperature window varies a little across climate zones, depending on what temperatures are common in those regions.
• When temperatures rose or fell from the feel-good temperature margin, online hate increased up to 12% for colder temperatures and up to 22% for hotter temperatures.
• The United Nations defines hate speech as cases of discriminatory language with reference to a person or a group on the basis of their religion, ethnicity, nationality, race, color, descent, gender, or other identity factor.
• The consequences of more aggressive online behavior can be severe, as hate speech has been found to have negative effects on the mental health of online hate victims, especially for young people and marginalized groups. It can also be predictive of hate crimes in the offline world.

A version of this article first appeared on Medscape.com.

This is a summary of the article, “Temperature Impacts on Hate Speech Online: Evidence From Four Billion Tweets,” published by The Lancet Planetary Health on September 1, 2022. The full article can be found on thelancet.com.

Extreme hot or cold temperatures shifts may trigger a rise in hate speech on social media, according to researchers from the Potsdam Institute for Climate Impact Research.

What to know

• Analyzing over four billion tweets posted on the social media platform Twitter in the United States, researchers found that hate speech increased across climate zones, income groups, and belief systems when temperatures were too hot or too cold outside.
• The minimum number of hate tweets appears to occur when temperatures are between 15° and 18° C (59° to 65° F). The precise feel-good temperature window varies a little across climate zones, depending on what temperatures are common in those regions.
• When temperatures rose or fell from the feel-good temperature margin, online hate increased up to 12% for colder temperatures and up to 22% for hotter temperatures.
• The United Nations defines hate speech as cases of discriminatory language with reference to a person or a group on the basis of their religion, ethnicity, nationality, race, color, descent, gender, or other identity factor.
• The consequences of more aggressive online behavior can be severe, as hate speech has been found to have negative effects on the mental health of online hate victims, especially for young people and marginalized groups. It can also be predictive of hate crimes in the offline world.

A version of this article first appeared on Medscape.com.

This is a summary of the article, “Temperature Impacts on Hate Speech Online: Evidence From Four Billion Tweets,” published by The Lancet Planetary Health on September 1, 2022. The full article can be found on thelancet.com.

Extreme hot or cold temperatures shifts may trigger a rise in hate speech on social media, according to researchers from the Potsdam Institute for Climate Impact Research.

What to know

• Analyzing over four billion tweets posted on the social media platform Twitter in the United States, researchers found that hate speech increased across climate zones, income groups, and belief systems when temperatures were too hot or too cold outside.
• The minimum number of hate tweets appears to occur when temperatures are between 15° and 18° C (59° to 65° F). The precise feel-good temperature window varies a little across climate zones, depending on what temperatures are common in those regions.
• When temperatures rose or fell from the feel-good temperature margin, online hate increased up to 12% for colder temperatures and up to 22% for hotter temperatures.
• The United Nations defines hate speech as cases of discriminatory language with reference to a person or a group on the basis of their religion, ethnicity, nationality, race, color, descent, gender, or other identity factor.
• The consequences of more aggressive online behavior can be severe, as hate speech has been found to have negative effects on the mental health of online hate victims, especially for young people and marginalized groups. It can also be predictive of hate crimes in the offline world.

A version of this article first appeared on Medscape.com.

This is a summary of the article, “Temperature Impacts on Hate Speech Online: Evidence From Four Billion Tweets,” published by The Lancet Planetary Health on September 1, 2022. The full article can be found on thelancet.com.

ORLANDO – Using a low-chloride, balanced crystalloid solution for all intravenous fluids received by patients who received a deceased donor kidney transplant resulted in significantly fewer episodes of delayed graft function, compared with patients who received saline as their IV fluids, in a new multicenter trial with 807 randomized and evaluable patients called BEST-Fluids.

“The findings suggest that balanced crystalloids should be the standard-of-care IV fluid in deceased donor kidney transplantations,” Michael G. Collins, MBChB, PhD, said at the annual meeting of the American Society of Nephrology.

Mitchel L. Zoler/MDedge News

Treating 10 patients prevents one delayed graft function

The incidence of delayed graft function, defined as the need for dialysis during the 7 days following transplantation, occurred in 30.0% of 404 patients who received balanced crystalloid fluids (Plasma-Lyte 148) and in 39.7% of 403 patients who received saline starting at the time of randomization (prior to surgery) until 48 hours post-surgery, Dr. Collins reported.

This translated into a significant, adjusted relative risk reduction of 26% and a number needed to treat of 10 to result in one avoided episode of delayed graft function.

Preventing delayed graft function is important because it is a “major complication” of deceased donor kidney transplantation that usually occurs in about 30%-50% of people who receive these organs, Dr. Collins explained. Incident delayed graft function leads to higher hospitalization costs because of a prolonged need for dialysis and extended hospital days, as well as increased risk for long-term graft failure and death.

A secondary outcome – the number of dialysis sessions required during the 28 days following transplantation – was 406 sessions among those who received balanced crystalloid fluids and 596 sessions among the controls who received saline, a significant adjusted relative decrease of 30%.

Freedom from need for dialysis by 12 weeks after surgery increased by a significant 10% among those treated with balanced crystalloid fluids, compared with controls. The balanced crystalloid fluids were also significantly linked with an average 1-L increase in urine output during the first 2 days after transplantation, compared with controls.
 

Chloride is the culprit

“I think this is driven by the harmful effects of saline,” which is currently the standard fluid that kidney transplant patients receive worldwide, said Dr. Collins. Specifically, he cited the chloride content of saline – which contains 0.9% sodium chloride – as the culprit by causing reduced kidney perfusion.

“Some data suggest that saline may be harmful because of chloride acidosis producing vasoconstriction and increasing ischemia,” commented Karen A. Griffin, MD, chief of the renal section at the Edward Hines, Jr. VA Medical Center, Hines, Illinois. But Dr. Griffin said she’d like to see further study of balanced crystalloid fluids in this setting before she’d be comfortable using it routinely as a replacement for saline.

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

Success attributed to early treatment

But Dr. Lafayette also wondered, “Why should this work for transplant patients when it did not work for patients who develop acute kidney injury in the ICU?” And he found it hard to understand how the impact of the balanced crystalloid fluid could manifest so quickly, with a change in urine output during the first day following surgery.

Dr. Collins attributed the rapid effects and overall success to the early initiation of balanced crystalloid fluids before the transplant occurred.   

The BEST-Fluids trial ran at 16 centers in Australia and New Zealand and enrolled patients from January 2018 to August 2020. It enrolled adults and children scheduled to receive a deceased donor kidney, excluding those who weighed less than 20 kg and those who received multiple organs.

Enrolled patients averaged about 55 years old, about 63% were men, and their average duration on dialysis prior to surgery was about 30 months. The study randomized 808 patients who received their transplanted kidney, with 807 included in the efficacy analysis. Patients in each of the two groups showed very close balance for all reported parameters of patient and donor characteristics. During the period of randomized fluid treatment, patients in the balanced crystalloid group received an average of just over 8 L of fluid, while those in the control group received an average of just over 7 L.

During follow-up, serious adverse events were rare and balanced, with three in the balanced crystalloid group and four among controls.

The only significant difference in adverse events was the rate of ICU admissions that required ventilation, which occurred in one patient in the balanced crystalloid group and 12 controls.

BEST-Fluids received balanced crystalloid and saline solutions at no charge from Baxter Healthcare, which markets Plasma-Lyte 148. The study received no other commercial funding. Dr. Collins, Dr. Griffin, and Dr. Lane have reported no relevant financial relationships. Dr. Lafayette has received personal fees and grants from Alexion, Aurinia, Calliditas, Omeros, Pfizer, Roche, Travere, and Vera and has been an advisor to Akahest and Equillium.

A version of this article first appeared on Medscape.com.

ORLANDO – Using a low-chloride, balanced crystalloid solution for all intravenous fluids received by patients who received a deceased donor kidney transplant resulted in significantly fewer episodes of delayed graft function, compared with patients who received saline as their IV fluids, in a new multicenter trial with 807 randomized and evaluable patients called BEST-Fluids.

“The findings suggest that balanced crystalloids should be the standard-of-care IV fluid in deceased donor kidney transplantations,” Michael G. Collins, MBChB, PhD, said at the annual meeting of the American Society of Nephrology.

Mitchel L. Zoler/MDedge News

Treating 10 patients prevents one delayed graft function

The incidence of delayed graft function, defined as the need for dialysis during the 7 days following transplantation, occurred in 30.0% of 404 patients who received balanced crystalloid fluids (Plasma-Lyte 148) and in 39.7% of 403 patients who received saline starting at the time of randomization (prior to surgery) until 48 hours post-surgery, Dr. Collins reported.

This translated into a significant, adjusted relative risk reduction of 26% and a number needed to treat of 10 to result in one avoided episode of delayed graft function.

Preventing delayed graft function is important because it is a “major complication” of deceased donor kidney transplantation that usually occurs in about 30%-50% of people who receive these organs, Dr. Collins explained. Incident delayed graft function leads to higher hospitalization costs because of a prolonged need for dialysis and extended hospital days, as well as increased risk for long-term graft failure and death.

A secondary outcome – the number of dialysis sessions required during the 28 days following transplantation – was 406 sessions among those who received balanced crystalloid fluids and 596 sessions among the controls who received saline, a significant adjusted relative decrease of 30%.

Freedom from need for dialysis by 12 weeks after surgery increased by a significant 10% among those treated with balanced crystalloid fluids, compared with controls. The balanced crystalloid fluids were also significantly linked with an average 1-L increase in urine output during the first 2 days after transplantation, compared with controls.
 

Chloride is the culprit

“I think this is driven by the harmful effects of saline,” which is currently the standard fluid that kidney transplant patients receive worldwide, said Dr. Collins. Specifically, he cited the chloride content of saline – which contains 0.9% sodium chloride – as the culprit by causing reduced kidney perfusion.

“Some data suggest that saline may be harmful because of chloride acidosis producing vasoconstriction and increasing ischemia,” commented Karen A. Griffin, MD, chief of the renal section at the Edward Hines, Jr. VA Medical Center, Hines, Illinois. But Dr. Griffin said she’d like to see further study of balanced crystalloid fluids in this setting before she’d be comfortable using it routinely as a replacement for saline.

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

Success attributed to early treatment

But Dr. Lafayette also wondered, “Why should this work for transplant patients when it did not work for patients who develop acute kidney injury in the ICU?” And he found it hard to understand how the impact of the balanced crystalloid fluid could manifest so quickly, with a change in urine output during the first day following surgery.

Dr. Collins attributed the rapid effects and overall success to the early initiation of balanced crystalloid fluids before the transplant occurred.   

The BEST-Fluids trial ran at 16 centers in Australia and New Zealand and enrolled patients from January 2018 to August 2020. It enrolled adults and children scheduled to receive a deceased donor kidney, excluding those who weighed less than 20 kg and those who received multiple organs.

Enrolled patients averaged about 55 years old, about 63% were men, and their average duration on dialysis prior to surgery was about 30 months. The study randomized 808 patients who received their transplanted kidney, with 807 included in the efficacy analysis. Patients in each of the two groups showed very close balance for all reported parameters of patient and donor characteristics. During the period of randomized fluid treatment, patients in the balanced crystalloid group received an average of just over 8 L of fluid, while those in the control group received an average of just over 7 L.

During follow-up, serious adverse events were rare and balanced, with three in the balanced crystalloid group and four among controls.

The only significant difference in adverse events was the rate of ICU admissions that required ventilation, which occurred in one patient in the balanced crystalloid group and 12 controls.

BEST-Fluids received balanced crystalloid and saline solutions at no charge from Baxter Healthcare, which markets Plasma-Lyte 148. The study received no other commercial funding. Dr. Collins, Dr. Griffin, and Dr. Lane have reported no relevant financial relationships. Dr. Lafayette has received personal fees and grants from Alexion, Aurinia, Calliditas, Omeros, Pfizer, Roche, Travere, and Vera and has been an advisor to Akahest and Equillium.

A version of this article first appeared on Medscape.com.

ORLANDO – Using a low-chloride, balanced crystalloid solution for all intravenous fluids received by patients who received a deceased donor kidney transplant resulted in significantly fewer episodes of delayed graft function, compared with patients who received saline as their IV fluids, in a new multicenter trial with 807 randomized and evaluable patients called BEST-Fluids.

“The findings suggest that balanced crystalloids should be the standard-of-care IV fluid in deceased donor kidney transplantations,” Michael G. Collins, MBChB, PhD, said at the annual meeting of the American Society of Nephrology.

Mitchel L. Zoler/MDedge News

Treating 10 patients prevents one delayed graft function

The incidence of delayed graft function, defined as the need for dialysis during the 7 days following transplantation, occurred in 30.0% of 404 patients who received balanced crystalloid fluids (Plasma-Lyte 148) and in 39.7% of 403 patients who received saline starting at the time of randomization (prior to surgery) until 48 hours post-surgery, Dr. Collins reported.

This translated into a significant, adjusted relative risk reduction of 26% and a number needed to treat of 10 to result in one avoided episode of delayed graft function.

Preventing delayed graft function is important because it is a “major complication” of deceased donor kidney transplantation that usually occurs in about 30%-50% of people who receive these organs, Dr. Collins explained. Incident delayed graft function leads to higher hospitalization costs because of a prolonged need for dialysis and extended hospital days, as well as increased risk for long-term graft failure and death.

A secondary outcome – the number of dialysis sessions required during the 28 days following transplantation – was 406 sessions among those who received balanced crystalloid fluids and 596 sessions among the controls who received saline, a significant adjusted relative decrease of 30%.

Freedom from need for dialysis by 12 weeks after surgery increased by a significant 10% among those treated with balanced crystalloid fluids, compared with controls. The balanced crystalloid fluids were also significantly linked with an average 1-L increase in urine output during the first 2 days after transplantation, compared with controls.
 

Chloride is the culprit

“I think this is driven by the harmful effects of saline,” which is currently the standard fluid that kidney transplant patients receive worldwide, said Dr. Collins. Specifically, he cited the chloride content of saline – which contains 0.9% sodium chloride – as the culprit by causing reduced kidney perfusion.

“Some data suggest that saline may be harmful because of chloride acidosis producing vasoconstriction and increasing ischemia,” commented Karen A. Griffin, MD, chief of the renal section at the Edward Hines, Jr. VA Medical Center, Hines, Illinois. But Dr. Griffin said she’d like to see further study of balanced crystalloid fluids in this setting before she’d be comfortable using it routinely as a replacement for saline.

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

Success attributed to early treatment

But Dr. Lafayette also wondered, “Why should this work for transplant patients when it did not work for patients who develop acute kidney injury in the ICU?” And he found it hard to understand how the impact of the balanced crystalloid fluid could manifest so quickly, with a change in urine output during the first day following surgery.

Dr. Collins attributed the rapid effects and overall success to the early initiation of balanced crystalloid fluids before the transplant occurred.   

The BEST-Fluids trial ran at 16 centers in Australia and New Zealand and enrolled patients from January 2018 to August 2020. It enrolled adults and children scheduled to receive a deceased donor kidney, excluding those who weighed less than 20 kg and those who received multiple organs.

Enrolled patients averaged about 55 years old, about 63% were men, and their average duration on dialysis prior to surgery was about 30 months. The study randomized 808 patients who received their transplanted kidney, with 807 included in the efficacy analysis. Patients in each of the two groups showed very close balance for all reported parameters of patient and donor characteristics. During the period of randomized fluid treatment, patients in the balanced crystalloid group received an average of just over 8 L of fluid, while those in the control group received an average of just over 7 L.

During follow-up, serious adverse events were rare and balanced, with three in the balanced crystalloid group and four among controls.

The only significant difference in adverse events was the rate of ICU admissions that required ventilation, which occurred in one patient in the balanced crystalloid group and 12 controls.

BEST-Fluids received balanced crystalloid and saline solutions at no charge from Baxter Healthcare, which markets Plasma-Lyte 148. The study received no other commercial funding. Dr. Collins, Dr. Griffin, and Dr. Lane have reported no relevant financial relationships. Dr. Lafayette has received personal fees and grants from Alexion, Aurinia, Calliditas, Omeros, Pfizer, Roche, Travere, and Vera and has been an advisor to Akahest and Equillium.

A version of this article first appeared on Medscape.com.

You only are free when you realize you belong no place – you belong every place – no place at all. The price is high. The reward is great. ~ Maya Angelou

At 8 o’clock, every weekday morning, for years and years now, two friends appear in my kitchen for coffee, and so one identity I carry includes being part of the “coffee ladies.” While this is one of the smaller and more intimate groups to which I belong, I am also a member (“distinguished,” no less) of a slightly larger group: the American Psychiatric Association, and being part of both groups is meaningful to me in more ways than I can describe.

When I think back over the years, I – like most people – have belonged to many people and places, either officially or unofficially. It is these connections that define us, fill our time, give us meaning and purpose, and anchor us. We belong to our families and friends, but we also belong to our professional and community groups, our institutions – whether they are hospitals, schools, religious centers, country clubs, or charitable organizations – as well as interest and advocacy groups. And finally, we belong to our coworkers and to our patients, and they to us, especially if we see the same people over time. Being a psychiatrist can be a solitary career, and it can take a little effort to be a part of larger worlds, especially for those who find solace in more individual activities.

As I’ve gotten older, I’ve noticed that I belong to fewer of these groups. I’m no longer a little league or field hockey mom, nor a member of the neighborhood babysitting co-op, and I’ve exhausted the gamut of council and leadership positions in my APA district branch. I’ve joined organizations only to pay the membership fee, and then never gone to their meetings or events. The pandemic has accounted for some of this: I still belong to my book club, but I often read the book and don’t go to the Zoom meetings as I miss the real-life aspect of getting together. Being boxed on a screen is not the same as the one-on-one conversations before the formal book discussion. And while I still carry a host of identities, I imagine it is not unusual to belong to fewer organizations as time passes. It’s not all bad, there is something good to be said for living life at a less frenetic pace as fewer entities lay claim to my time.

In psychiatry, our patients span the range of human experience: Some are very engaged with their worlds, while others struggle to make even the most basic of connections. Their lives may seem disconnected – empty, even – and I find myself encouraging people to reach out, to find activities that will ease their loneliness and integrate a feeling of belonging in a way that adds meaning and purpose. For some people, this may be as simple as asking a friend to have lunch, but even that can be an overwhelming obstacle for someone who is depressed, or for someone who has no friends.

Patients may counter my suggestions with a host of reasons as to why they can’t connect. Perhaps their friend is too busy with work or his family, the lunch would cost too much, there’s no transportation, or no restaurant that could meet their dietary needs. Or perhaps they are just too fearful of being rejected.

Psychiatric disorders, by their nature, can be very isolating. Depressed and anxious people often find it a struggle just to get through their days, adding new people and activities is not something that brings joy. For people suffering with psychosis, their internal realities are often all-consuming and there may be no room for accommodating others. And finally, what I hear over and over, is that people are afraid of what others might think of them, and this fear is paralyzing. I try to suggest that we never really know or control what others think of us, but obviously, this does not reassure most patients as they are also bewildered by their irrational fear. To go to an event unaccompanied, or even to a party to which they have been invited, is a hurdle they won’t (or can’t) attempt.

The pandemic, with its initial months of shutdown, and then with years of fear of illness, has created new ways of connecting. Our “Zoom” world can be very convenient – in many ways it has opened up aspects of learning and connection for people who are short on time,or struggle with transportation. In the comfort of our living rooms, in pajamas and slippers, we can take classes, join clubs, attend Alcoholics Anonymous meetings, go to conferences or religious services, and be part of any number of organizations without flying or searching for parking. I love that, with 1 hour and a single click, I can now attend my department’s weekly Grand Rounds. But for many who struggle with using technology, or who don’t feel the same benefits from online encounters, the pandemic has been an isolating and lonely time.

It should not be assumed that isolation has been a negative experience for everyone. For many who struggle with interpersonal relationships, for children who are bullied or teased at school or who feel self-conscious sitting alone at lunch, there may not be the presumed “fear of missing out.” As one adult patient told me: “You know, I do ‘alone’ well.” For some, it has been a relief to be relieved of the pressure to socialize, attend parties, or pursue online dating – a process I think of as “people-shopping” which looks so different from the old days of organic interactions that led to romantic interactions over time. Many have found relief without the pressures of social interactions.

Community, connection, and belonging are not inconsequential things, however. They are part of what adds to life’s richness, and they are associated with good health and longevity. The Harvard Study of Adult Development, begun in 1938, has been tracking two groups of Boston teenagers – and now their wives and children – for 84 years. Tracking one group of Harvard students and another group of teens from poorer areas in Boston, the project is now on its 4th director.

George Vaillant, MD, author of “Aging Well: Surprising Guideposts to a Happier Life from the Landmark Harvard Study of Adult Development” (New York: Little, Brown Spark, 2002) was the program’s director from 1972 to 2004. “When the study began, nobody cared about empathy or attachment. But the key to healthy aging is relationships, relationships, relationships,” Dr. Vaillant said in an interview in the Harvard Gazette.

Susan Pinker is a social psychologist and author of “The Village Effect: How Face-to-Face Contact Can Make Us Healthier and Happier” (Toronto: Random House Canada, 2014). In her 2017 TED talk, she notes that in all developed countries, women live 6-8 years longer than men, and are half as likely to die at any age. She is underwhelmed by digital relationships, and says that real life relationships affect our physiological states differently and in more beneficial ways. “Building your village and sustaining it is a matter of life and death,” she states at the end of her TED talk.

I spoke with Ms. Pinker about her thoughts on how our personal villages change over time. She was quick to tell me that she is not against digital communities. “I’m not a Luddite. As a writer, I probably spend as much time facing a screen as anyone else. But it’s important to remember that digital communities can amplify existing relationships, and don’t replace in-person social contact. A lot of people have drunk the Kool-Aid about virtual experiences, even though they are not the same as real life interactions.

“Loneliness takes on a U-shaped function across adulthood,” she explained with regard to how age impacts our social connections. “People are lonely when they first leave home or when they finish college and go out into the world. Then they settle into new situations; they can make friends at work, through their children, in their neighborhood, or by belonging to organizations. As people settle into their adult lives, there are increased opportunities to connect in person. But loneliness increases again in late middle age.” She explained that everyone loses people as their children move away, friends move, and couples may divorce or a spouse dies.

“Attrition of our social face-to-face networks is an ugly feature of aging,” Ms. Pinker said. “Some people are good at replacing the vacant spots; they sense that it is important to invest in different relationships as you age. It’s like a garden that you need to tend by replacing the perennials that die off in the winter.” The United States, she pointed out, has a culture that is particularly difficult for people in their later years.

My world is a little quieter than it once was, but collecting and holding on to people is important to me. The organizations and affiliations change over time, as does the brand of coffee. So I try to inspire some of my more isolated patients to prioritize their relationships, to let go of their grudges, to tolerate the discomfort of moving from their places of comfort to the temporary discomfort of reaching out in the service of achieving a less solitary, more purposeful, and healthier life. When it doesn’t come naturally, it can be hard work.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

You only are free when you realize you belong no place – you belong every place – no place at all. The price is high. The reward is great. ~ Maya Angelou

At 8 o’clock, every weekday morning, for years and years now, two friends appear in my kitchen for coffee, and so one identity I carry includes being part of the “coffee ladies.” While this is one of the smaller and more intimate groups to which I belong, I am also a member (“distinguished,” no less) of a slightly larger group: the American Psychiatric Association, and being part of both groups is meaningful to me in more ways than I can describe.

When I think back over the years, I – like most people – have belonged to many people and places, either officially or unofficially. It is these connections that define us, fill our time, give us meaning and purpose, and anchor us. We belong to our families and friends, but we also belong to our professional and community groups, our institutions – whether they are hospitals, schools, religious centers, country clubs, or charitable organizations – as well as interest and advocacy groups. And finally, we belong to our coworkers and to our patients, and they to us, especially if we see the same people over time. Being a psychiatrist can be a solitary career, and it can take a little effort to be a part of larger worlds, especially for those who find solace in more individual activities.

As I’ve gotten older, I’ve noticed that I belong to fewer of these groups. I’m no longer a little league or field hockey mom, nor a member of the neighborhood babysitting co-op, and I’ve exhausted the gamut of council and leadership positions in my APA district branch. I’ve joined organizations only to pay the membership fee, and then never gone to their meetings or events. The pandemic has accounted for some of this: I still belong to my book club, but I often read the book and don’t go to the Zoom meetings as I miss the real-life aspect of getting together. Being boxed on a screen is not the same as the one-on-one conversations before the formal book discussion. And while I still carry a host of identities, I imagine it is not unusual to belong to fewer organizations as time passes. It’s not all bad, there is something good to be said for living life at a less frenetic pace as fewer entities lay claim to my time.

In psychiatry, our patients span the range of human experience: Some are very engaged with their worlds, while others struggle to make even the most basic of connections. Their lives may seem disconnected – empty, even – and I find myself encouraging people to reach out, to find activities that will ease their loneliness and integrate a feeling of belonging in a way that adds meaning and purpose. For some people, this may be as simple as asking a friend to have lunch, but even that can be an overwhelming obstacle for someone who is depressed, or for someone who has no friends.

Patients may counter my suggestions with a host of reasons as to why they can’t connect. Perhaps their friend is too busy with work or his family, the lunch would cost too much, there’s no transportation, or no restaurant that could meet their dietary needs. Or perhaps they are just too fearful of being rejected.

Psychiatric disorders, by their nature, can be very isolating. Depressed and anxious people often find it a struggle just to get through their days, adding new people and activities is not something that brings joy. For people suffering with psychosis, their internal realities are often all-consuming and there may be no room for accommodating others. And finally, what I hear over and over, is that people are afraid of what others might think of them, and this fear is paralyzing. I try to suggest that we never really know or control what others think of us, but obviously, this does not reassure most patients as they are also bewildered by their irrational fear. To go to an event unaccompanied, or even to a party to which they have been invited, is a hurdle they won’t (or can’t) attempt.

The pandemic, with its initial months of shutdown, and then with years of fear of illness, has created new ways of connecting. Our “Zoom” world can be very convenient – in many ways it has opened up aspects of learning and connection for people who are short on time,or struggle with transportation. In the comfort of our living rooms, in pajamas and slippers, we can take classes, join clubs, attend Alcoholics Anonymous meetings, go to conferences or religious services, and be part of any number of organizations without flying or searching for parking. I love that, with 1 hour and a single click, I can now attend my department’s weekly Grand Rounds. But for many who struggle with using technology, or who don’t feel the same benefits from online encounters, the pandemic has been an isolating and lonely time.

It should not be assumed that isolation has been a negative experience for everyone. For many who struggle with interpersonal relationships, for children who are bullied or teased at school or who feel self-conscious sitting alone at lunch, there may not be the presumed “fear of missing out.” As one adult patient told me: “You know, I do ‘alone’ well.” For some, it has been a relief to be relieved of the pressure to socialize, attend parties, or pursue online dating – a process I think of as “people-shopping” which looks so different from the old days of organic interactions that led to romantic interactions over time. Many have found relief without the pressures of social interactions.

Community, connection, and belonging are not inconsequential things, however. They are part of what adds to life’s richness, and they are associated with good health and longevity. The Harvard Study of Adult Development, begun in 1938, has been tracking two groups of Boston teenagers – and now their wives and children – for 84 years. Tracking one group of Harvard students and another group of teens from poorer areas in Boston, the project is now on its 4th director.

George Vaillant, MD, author of “Aging Well: Surprising Guideposts to a Happier Life from the Landmark Harvard Study of Adult Development” (New York: Little, Brown Spark, 2002) was the program’s director from 1972 to 2004. “When the study began, nobody cared about empathy or attachment. But the key to healthy aging is relationships, relationships, relationships,” Dr. Vaillant said in an interview in the Harvard Gazette.

Susan Pinker is a social psychologist and author of “The Village Effect: How Face-to-Face Contact Can Make Us Healthier and Happier” (Toronto: Random House Canada, 2014). In her 2017 TED talk, she notes that in all developed countries, women live 6-8 years longer than men, and are half as likely to die at any age. She is underwhelmed by digital relationships, and says that real life relationships affect our physiological states differently and in more beneficial ways. “Building your village and sustaining it is a matter of life and death,” she states at the end of her TED talk.

I spoke with Ms. Pinker about her thoughts on how our personal villages change over time. She was quick to tell me that she is not against digital communities. “I’m not a Luddite. As a writer, I probably spend as much time facing a screen as anyone else. But it’s important to remember that digital communities can amplify existing relationships, and don’t replace in-person social contact. A lot of people have drunk the Kool-Aid about virtual experiences, even though they are not the same as real life interactions.

“Loneliness takes on a U-shaped function across adulthood,” she explained with regard to how age impacts our social connections. “People are lonely when they first leave home or when they finish college and go out into the world. Then they settle into new situations; they can make friends at work, through their children, in their neighborhood, or by belonging to organizations. As people settle into their adult lives, there are increased opportunities to connect in person. But loneliness increases again in late middle age.” She explained that everyone loses people as their children move away, friends move, and couples may divorce or a spouse dies.

“Attrition of our social face-to-face networks is an ugly feature of aging,” Ms. Pinker said. “Some people are good at replacing the vacant spots; they sense that it is important to invest in different relationships as you age. It’s like a garden that you need to tend by replacing the perennials that die off in the winter.” The United States, she pointed out, has a culture that is particularly difficult for people in their later years.

My world is a little quieter than it once was, but collecting and holding on to people is important to me. The organizations and affiliations change over time, as does the brand of coffee. So I try to inspire some of my more isolated patients to prioritize their relationships, to let go of their grudges, to tolerate the discomfort of moving from their places of comfort to the temporary discomfort of reaching out in the service of achieving a less solitary, more purposeful, and healthier life. When it doesn’t come naturally, it can be hard work.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

You only are free when you realize you belong no place – you belong every place – no place at all. The price is high. The reward is great. ~ Maya Angelou

At 8 o’clock, every weekday morning, for years and years now, two friends appear in my kitchen for coffee, and so one identity I carry includes being part of the “coffee ladies.” While this is one of the smaller and more intimate groups to which I belong, I am also a member (“distinguished,” no less) of a slightly larger group: the American Psychiatric Association, and being part of both groups is meaningful to me in more ways than I can describe.

When I think back over the years, I – like most people – have belonged to many people and places, either officially or unofficially. It is these connections that define us, fill our time, give us meaning and purpose, and anchor us. We belong to our families and friends, but we also belong to our professional and community groups, our institutions – whether they are hospitals, schools, religious centers, country clubs, or charitable organizations – as well as interest and advocacy groups. And finally, we belong to our coworkers and to our patients, and they to us, especially if we see the same people over time. Being a psychiatrist can be a solitary career, and it can take a little effort to be a part of larger worlds, especially for those who find solace in more individual activities.

As I’ve gotten older, I’ve noticed that I belong to fewer of these groups. I’m no longer a little league or field hockey mom, nor a member of the neighborhood babysitting co-op, and I’ve exhausted the gamut of council and leadership positions in my APA district branch. I’ve joined organizations only to pay the membership fee, and then never gone to their meetings or events. The pandemic has accounted for some of this: I still belong to my book club, but I often read the book and don’t go to the Zoom meetings as I miss the real-life aspect of getting together. Being boxed on a screen is not the same as the one-on-one conversations before the formal book discussion. And while I still carry a host of identities, I imagine it is not unusual to belong to fewer organizations as time passes. It’s not all bad, there is something good to be said for living life at a less frenetic pace as fewer entities lay claim to my time.

In psychiatry, our patients span the range of human experience: Some are very engaged with their worlds, while others struggle to make even the most basic of connections. Their lives may seem disconnected – empty, even – and I find myself encouraging people to reach out, to find activities that will ease their loneliness and integrate a feeling of belonging in a way that adds meaning and purpose. For some people, this may be as simple as asking a friend to have lunch, but even that can be an overwhelming obstacle for someone who is depressed, or for someone who has no friends.

Patients may counter my suggestions with a host of reasons as to why they can’t connect. Perhaps their friend is too busy with work or his family, the lunch would cost too much, there’s no transportation, or no restaurant that could meet their dietary needs. Or perhaps they are just too fearful of being rejected.

Psychiatric disorders, by their nature, can be very isolating. Depressed and anxious people often find it a struggle just to get through their days, adding new people and activities is not something that brings joy. For people suffering with psychosis, their internal realities are often all-consuming and there may be no room for accommodating others. And finally, what I hear over and over, is that people are afraid of what others might think of them, and this fear is paralyzing. I try to suggest that we never really know or control what others think of us, but obviously, this does not reassure most patients as they are also bewildered by their irrational fear. To go to an event unaccompanied, or even to a party to which they have been invited, is a hurdle they won’t (or can’t) attempt.

The pandemic, with its initial months of shutdown, and then with years of fear of illness, has created new ways of connecting. Our “Zoom” world can be very convenient – in many ways it has opened up aspects of learning and connection for people who are short on time,or struggle with transportation. In the comfort of our living rooms, in pajamas and slippers, we can take classes, join clubs, attend Alcoholics Anonymous meetings, go to conferences or religious services, and be part of any number of organizations without flying or searching for parking. I love that, with 1 hour and a single click, I can now attend my department’s weekly Grand Rounds. But for many who struggle with using technology, or who don’t feel the same benefits from online encounters, the pandemic has been an isolating and lonely time.

It should not be assumed that isolation has been a negative experience for everyone. For many who struggle with interpersonal relationships, for children who are bullied or teased at school or who feel self-conscious sitting alone at lunch, there may not be the presumed “fear of missing out.” As one adult patient told me: “You know, I do ‘alone’ well.” For some, it has been a relief to be relieved of the pressure to socialize, attend parties, or pursue online dating – a process I think of as “people-shopping” which looks so different from the old days of organic interactions that led to romantic interactions over time. Many have found relief without the pressures of social interactions.

Community, connection, and belonging are not inconsequential things, however. They are part of what adds to life’s richness, and they are associated with good health and longevity. The Harvard Study of Adult Development, begun in 1938, has been tracking two groups of Boston teenagers – and now their wives and children – for 84 years. Tracking one group of Harvard students and another group of teens from poorer areas in Boston, the project is now on its 4th director.

George Vaillant, MD, author of “Aging Well: Surprising Guideposts to a Happier Life from the Landmark Harvard Study of Adult Development” (New York: Little, Brown Spark, 2002) was the program’s director from 1972 to 2004. “When the study began, nobody cared about empathy or attachment. But the key to healthy aging is relationships, relationships, relationships,” Dr. Vaillant said in an interview in the Harvard Gazette.

Susan Pinker is a social psychologist and author of “The Village Effect: How Face-to-Face Contact Can Make Us Healthier and Happier” (Toronto: Random House Canada, 2014). In her 2017 TED talk, she notes that in all developed countries, women live 6-8 years longer than men, and are half as likely to die at any age. She is underwhelmed by digital relationships, and says that real life relationships affect our physiological states differently and in more beneficial ways. “Building your village and sustaining it is a matter of life and death,” she states at the end of her TED talk.

I spoke with Ms. Pinker about her thoughts on how our personal villages change over time. She was quick to tell me that she is not against digital communities. “I’m not a Luddite. As a writer, I probably spend as much time facing a screen as anyone else. But it’s important to remember that digital communities can amplify existing relationships, and don’t replace in-person social contact. A lot of people have drunk the Kool-Aid about virtual experiences, even though they are not the same as real life interactions.

“Loneliness takes on a U-shaped function across adulthood,” she explained with regard to how age impacts our social connections. “People are lonely when they first leave home or when they finish college and go out into the world. Then they settle into new situations; they can make friends at work, through their children, in their neighborhood, or by belonging to organizations. As people settle into their adult lives, there are increased opportunities to connect in person. But loneliness increases again in late middle age.” She explained that everyone loses people as their children move away, friends move, and couples may divorce or a spouse dies.

“Attrition of our social face-to-face networks is an ugly feature of aging,” Ms. Pinker said. “Some people are good at replacing the vacant spots; they sense that it is important to invest in different relationships as you age. It’s like a garden that you need to tend by replacing the perennials that die off in the winter.” The United States, she pointed out, has a culture that is particularly difficult for people in their later years.

My world is a little quieter than it once was, but collecting and holding on to people is important to me. The organizations and affiliations change over time, as does the brand of coffee. So I try to inspire some of my more isolated patients to prioritize their relationships, to let go of their grudges, to tolerate the discomfort of moving from their places of comfort to the temporary discomfort of reaching out in the service of achieving a less solitary, more purposeful, and healthier life. When it doesn’t come naturally, it can be hard work.

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. She has disclosed no relevant financial relationships.

ORLANDO – Automated alerts sent to clinicians via patients’ electronic health records identified patients with diagnosable acute kidney injury (AKI) who were taking one or more medications that could potentially further worsen their renal function. This led to a significant increase in discontinuations of the problematic drugs and better clinical outcomes in a subgroup of patients in a new multicenter, randomized study with more than 5,000 participants.

“Automated alerts for AKI can increase the rate of cessation of potentially nephrotoxic medications without endangering patients,” said F. Perry Wilson, MD, at Kidney Week 2022, organized by the American Society of Nephrology.

Mitchel L Zoler, Medscape Medical News © 2022 WebMD, LLC

In addition, the study provides “limited evidence that these alerts change clinical practice,” said Dr. Wilson, a nephrologist and director of the clinical and translational research accelerator at Yale School of Medicine in New Haven, Conn.

“It was encouraging to get providers to change their behavior” by quickly stopping treatment with potentially nephrotoxic medications in patients with incident AKI. But the results also confirmed that “patient decision-support systems tend to not be panaceas,” Dr. Wilson explained in an interview. Instead, “they tend to marginally improve” patients’ clinical status.

“Our hope is that widespread use may make some difference on a population scale, but rarely are these game changers,” he admitted.

“This was a very nice study showing how we can leverage the EHR to look not only at drugs but also contrast agents to direct educational efforts aimed at clinicians about when to discontinue” these treatments, commented Karen A. Griffin, MD, who was not involved with the study.
 

A danger for alert fatigue

But the results also showed that more research is needed to better refine this approach, added Dr. Griffin, a professor at Loyola University Chicago, Maywood, Ill., and chief of the renal section at the Edward Hines Jr. VA Medical Center in Hines, Ill. And she expressed caution about expanding the alerts that clinicians receive “because of the potential for alert fatigue.”

Dr. Wilson also acknowledged the danger for alert fatigue. “We’re doing these studies to try to reduce the number of alerts,” he said. “Most clinicians say that if we could show an alert improves patient outcomes, they would embrace it.”

Dr. Wilson and associates designed their current study to evaluate an enhanced type of alert that not only warned clinicians that a patient had developed AKI but also gave them an option to potentially intervene by stopping treatment with a medication that could possibly exacerbate worsening renal function. This enhancement followed their experience in a 2021 study that tested a purely informational alert that gave physicians no guidance about what actions to take to more quickly resolve the AKI.

These findings plus results from other studies suggested that “purely informational alerts may not be enough. They need to be linked” to suggested changes in patient management, Dr. Wilson explained.
 

Targeting NSAIDS, RAAS inhibitors, and PPIs

The new study used automated EHR analysis to not only identify patients with incident AKI, but also to flag medications these patients were receiving from any of three classes suspected of worsening renal function: nonsteroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system (RAAS) inhibitors (which include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), and proton-pump inhibitors (PPIs).

“Our hypothesis was that giving clinicians actionable advice could significantly improve patient outcomes,” Dr. Wilson said. “NSAIDs are frequently discontinued” in patients who develop AKI. “RAAS inhibitors are sometimes discontinued,” although the benefit from doing this remains unproven and controversial. “PPIs are rarely discontinued,” and may be an underappreciated contributor to AKI by causing interstitial nephritis in some patients.

The prospective study included 5,060 adults admitted with a diagnosis of stage 1 AKI at any of four Yale-affiliated teaching hospitals who were also taking agents from at least one of the three targeted drug classes at the time of admission. Clinicians caring for 2,532 of these patients received an alert about the AKI diagnosis and use of the questionable medications, while those caring for the 2,528 control patients received no alert and delivered usual care.

The study excluded patients with higher-risk profiles, including those with extremely elevated serum creatinine levels at admission (4.0 mg/dL or higher), those recently treated with dialysis, and patients with end-stage kidney disease.

The study had two primary outcomes. One measured the impact of the intervention on stopping the targeted drugs. The second assessed the clinical effect of the intervention on progression of AKI to a higher stage, need for dialysis, or death during either the duration of hospitalization or during the first 14 days following randomization.
 

Overall, a 9% relative increase in discontinuations

In general, the intervention had a modest but significant effect on cessation of the targeted drug classes within 24 hours of sending the alert.

Overall, there was about a 58% discontinuation rate among controls and about a 62% discontinuation rate among patients managed using the alerts, a significant 9% relative increase in any drug discontinuation, Dr. Wilson reported.

Discontinuations of NSAIDs occurred at the highest rate, in about 80% of patients in both groups, and the intervention showed no significant effect on stopping agents from this class. Discontinuations of RAAS inhibitors showed the largest absolute difference in between-group effect, about a 10–percentage point increase that represented a significant 14% relative increase in stopping agents from this class. Discontinuations of PPIs occurred at the lowest rate, in roughly 20% of patients, but the alert intervention had the greatest impact by raising the relative rate of stopping by a significant 26% compared with controls.

Analysis of the effect of the intervention on the combined clinical outcome showed a less robust impact. The alerts produced no significant change in the clinical outcome overall, or in the use of NSAIDs or RAAS inhibitors. However, the change in use of PPIs following the alerts significantly linked with a 12% relative drop in the incidence of the combined clinical endpoint of progression of AKI to a higher stage, need for dialysis, or death.

The results were consistent across several prespecified subgroups based on parameters such as age, sex, and race, but these analyses showed a signal that the alerts were most helpful for patients who had serum creatinine levels at admission of less than 0.5 mg/dL.

Dr. Wilson speculated that the alerts might have been especially effective for these patients because their low creatinine levels might otherwise mask AKI onset.

A safety analysis showed no evidence that the alert interventions and drug cessations increased the incidence of any complications.
 

PPIs may distinguish ‘sicker’ patients

Dr. Wilson cited two potential explanations for why the tested alerts appeared most effective for patients taking a PPI at the time of admission. One is that PPIs are underappreciated as a contributor to AKI, a possibility supported by the low rates of discontinuation in both the control and intervention groups.

In addition, treatment with a PPI may be a marker of “sicker” patients who may have more to gain from quicker identification of their AKI. For example, 28% of the patients who were taking a PPI at admission were in the ICU when they entered the study compared with a 14% rate of ICU care among everyone else.

PPIs were also the most-used targeted drug class among enrolled patients, used by 65% at baseline, compared with 53% who were taking a RAAS inhibitor and about 31% who were taking an NSAID. About 6% of enrolled patients were taking agents from all three classes at baseline, and 36% were on treatment with agents from two of the classes.

The next step is to assess adding more refinement to the alert process, Dr. Wilson said. He and his associates are now running a study in which an AKI alert goes to a “kidney action team” that includes a trained clinician and a pharmacist. The team would review the patient who triggered the alert and quickly make an individualized assessment of the best intervention for resolving the AKI.

The study received no commercial funding. Dr. Wilson has received research funding from AstraZeneca, Boehringer Ingelheim, Vifor, and Whoop. Dr. Griffin has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ORLANDO – Automated alerts sent to clinicians via patients’ electronic health records identified patients with diagnosable acute kidney injury (AKI) who were taking one or more medications that could potentially further worsen their renal function. This led to a significant increase in discontinuations of the problematic drugs and better clinical outcomes in a subgroup of patients in a new multicenter, randomized study with more than 5,000 participants.

“Automated alerts for AKI can increase the rate of cessation of potentially nephrotoxic medications without endangering patients,” said F. Perry Wilson, MD, at Kidney Week 2022, organized by the American Society of Nephrology.

Mitchel L Zoler, Medscape Medical News © 2022 WebMD, LLC

In addition, the study provides “limited evidence that these alerts change clinical practice,” said Dr. Wilson, a nephrologist and director of the clinical and translational research accelerator at Yale School of Medicine in New Haven, Conn.

“It was encouraging to get providers to change their behavior” by quickly stopping treatment with potentially nephrotoxic medications in patients with incident AKI. But the results also confirmed that “patient decision-support systems tend to not be panaceas,” Dr. Wilson explained in an interview. Instead, “they tend to marginally improve” patients’ clinical status.

“Our hope is that widespread use may make some difference on a population scale, but rarely are these game changers,” he admitted.

“This was a very nice study showing how we can leverage the EHR to look not only at drugs but also contrast agents to direct educational efforts aimed at clinicians about when to discontinue” these treatments, commented Karen A. Griffin, MD, who was not involved with the study.
 

A danger for alert fatigue

But the results also showed that more research is needed to better refine this approach, added Dr. Griffin, a professor at Loyola University Chicago, Maywood, Ill., and chief of the renal section at the Edward Hines Jr. VA Medical Center in Hines, Ill. And she expressed caution about expanding the alerts that clinicians receive “because of the potential for alert fatigue.”

Dr. Wilson also acknowledged the danger for alert fatigue. “We’re doing these studies to try to reduce the number of alerts,” he said. “Most clinicians say that if we could show an alert improves patient outcomes, they would embrace it.”

Dr. Wilson and associates designed their current study to evaluate an enhanced type of alert that not only warned clinicians that a patient had developed AKI but also gave them an option to potentially intervene by stopping treatment with a medication that could possibly exacerbate worsening renal function. This enhancement followed their experience in a 2021 study that tested a purely informational alert that gave physicians no guidance about what actions to take to more quickly resolve the AKI.

These findings plus results from other studies suggested that “purely informational alerts may not be enough. They need to be linked” to suggested changes in patient management, Dr. Wilson explained.
 

Targeting NSAIDS, RAAS inhibitors, and PPIs

The new study used automated EHR analysis to not only identify patients with incident AKI, but also to flag medications these patients were receiving from any of three classes suspected of worsening renal function: nonsteroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system (RAAS) inhibitors (which include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), and proton-pump inhibitors (PPIs).

“Our hypothesis was that giving clinicians actionable advice could significantly improve patient outcomes,” Dr. Wilson said. “NSAIDs are frequently discontinued” in patients who develop AKI. “RAAS inhibitors are sometimes discontinued,” although the benefit from doing this remains unproven and controversial. “PPIs are rarely discontinued,” and may be an underappreciated contributor to AKI by causing interstitial nephritis in some patients.

The prospective study included 5,060 adults admitted with a diagnosis of stage 1 AKI at any of four Yale-affiliated teaching hospitals who were also taking agents from at least one of the three targeted drug classes at the time of admission. Clinicians caring for 2,532 of these patients received an alert about the AKI diagnosis and use of the questionable medications, while those caring for the 2,528 control patients received no alert and delivered usual care.

The study excluded patients with higher-risk profiles, including those with extremely elevated serum creatinine levels at admission (4.0 mg/dL or higher), those recently treated with dialysis, and patients with end-stage kidney disease.

The study had two primary outcomes. One measured the impact of the intervention on stopping the targeted drugs. The second assessed the clinical effect of the intervention on progression of AKI to a higher stage, need for dialysis, or death during either the duration of hospitalization or during the first 14 days following randomization.
 

Overall, a 9% relative increase in discontinuations

In general, the intervention had a modest but significant effect on cessation of the targeted drug classes within 24 hours of sending the alert.

Overall, there was about a 58% discontinuation rate among controls and about a 62% discontinuation rate among patients managed using the alerts, a significant 9% relative increase in any drug discontinuation, Dr. Wilson reported.

Discontinuations of NSAIDs occurred at the highest rate, in about 80% of patients in both groups, and the intervention showed no significant effect on stopping agents from this class. Discontinuations of RAAS inhibitors showed the largest absolute difference in between-group effect, about a 10–percentage point increase that represented a significant 14% relative increase in stopping agents from this class. Discontinuations of PPIs occurred at the lowest rate, in roughly 20% of patients, but the alert intervention had the greatest impact by raising the relative rate of stopping by a significant 26% compared with controls.

Analysis of the effect of the intervention on the combined clinical outcome showed a less robust impact. The alerts produced no significant change in the clinical outcome overall, or in the use of NSAIDs or RAAS inhibitors. However, the change in use of PPIs following the alerts significantly linked with a 12% relative drop in the incidence of the combined clinical endpoint of progression of AKI to a higher stage, need for dialysis, or death.

The results were consistent across several prespecified subgroups based on parameters such as age, sex, and race, but these analyses showed a signal that the alerts were most helpful for patients who had serum creatinine levels at admission of less than 0.5 mg/dL.

Dr. Wilson speculated that the alerts might have been especially effective for these patients because their low creatinine levels might otherwise mask AKI onset.

A safety analysis showed no evidence that the alert interventions and drug cessations increased the incidence of any complications.
 

PPIs may distinguish ‘sicker’ patients

Dr. Wilson cited two potential explanations for why the tested alerts appeared most effective for patients taking a PPI at the time of admission. One is that PPIs are underappreciated as a contributor to AKI, a possibility supported by the low rates of discontinuation in both the control and intervention groups.

In addition, treatment with a PPI may be a marker of “sicker” patients who may have more to gain from quicker identification of their AKI. For example, 28% of the patients who were taking a PPI at admission were in the ICU when they entered the study compared with a 14% rate of ICU care among everyone else.

PPIs were also the most-used targeted drug class among enrolled patients, used by 65% at baseline, compared with 53% who were taking a RAAS inhibitor and about 31% who were taking an NSAID. About 6% of enrolled patients were taking agents from all three classes at baseline, and 36% were on treatment with agents from two of the classes.

The next step is to assess adding more refinement to the alert process, Dr. Wilson said. He and his associates are now running a study in which an AKI alert goes to a “kidney action team” that includes a trained clinician and a pharmacist. The team would review the patient who triggered the alert and quickly make an individualized assessment of the best intervention for resolving the AKI.

The study received no commercial funding. Dr. Wilson has received research funding from AstraZeneca, Boehringer Ingelheim, Vifor, and Whoop. Dr. Griffin has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ORLANDO – Automated alerts sent to clinicians via patients’ electronic health records identified patients with diagnosable acute kidney injury (AKI) who were taking one or more medications that could potentially further worsen their renal function. This led to a significant increase in discontinuations of the problematic drugs and better clinical outcomes in a subgroup of patients in a new multicenter, randomized study with more than 5,000 participants.

“Automated alerts for AKI can increase the rate of cessation of potentially nephrotoxic medications without endangering patients,” said F. Perry Wilson, MD, at Kidney Week 2022, organized by the American Society of Nephrology.

Mitchel L Zoler, Medscape Medical News © 2022 WebMD, LLC

In addition, the study provides “limited evidence that these alerts change clinical practice,” said Dr. Wilson, a nephrologist and director of the clinical and translational research accelerator at Yale School of Medicine in New Haven, Conn.

“It was encouraging to get providers to change their behavior” by quickly stopping treatment with potentially nephrotoxic medications in patients with incident AKI. But the results also confirmed that “patient decision-support systems tend to not be panaceas,” Dr. Wilson explained in an interview. Instead, “they tend to marginally improve” patients’ clinical status.

“Our hope is that widespread use may make some difference on a population scale, but rarely are these game changers,” he admitted.

“This was a very nice study showing how we can leverage the EHR to look not only at drugs but also contrast agents to direct educational efforts aimed at clinicians about when to discontinue” these treatments, commented Karen A. Griffin, MD, who was not involved with the study.
 

A danger for alert fatigue

But the results also showed that more research is needed to better refine this approach, added Dr. Griffin, a professor at Loyola University Chicago, Maywood, Ill., and chief of the renal section at the Edward Hines Jr. VA Medical Center in Hines, Ill. And she expressed caution about expanding the alerts that clinicians receive “because of the potential for alert fatigue.”

Dr. Wilson also acknowledged the danger for alert fatigue. “We’re doing these studies to try to reduce the number of alerts,” he said. “Most clinicians say that if we could show an alert improves patient outcomes, they would embrace it.”

Dr. Wilson and associates designed their current study to evaluate an enhanced type of alert that not only warned clinicians that a patient had developed AKI but also gave them an option to potentially intervene by stopping treatment with a medication that could possibly exacerbate worsening renal function. This enhancement followed their experience in a 2021 study that tested a purely informational alert that gave physicians no guidance about what actions to take to more quickly resolve the AKI.

These findings plus results from other studies suggested that “purely informational alerts may not be enough. They need to be linked” to suggested changes in patient management, Dr. Wilson explained.
 

Targeting NSAIDS, RAAS inhibitors, and PPIs

The new study used automated EHR analysis to not only identify patients with incident AKI, but also to flag medications these patients were receiving from any of three classes suspected of worsening renal function: nonsteroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system (RAAS) inhibitors (which include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), and proton-pump inhibitors (PPIs).

“Our hypothesis was that giving clinicians actionable advice could significantly improve patient outcomes,” Dr. Wilson said. “NSAIDs are frequently discontinued” in patients who develop AKI. “RAAS inhibitors are sometimes discontinued,” although the benefit from doing this remains unproven and controversial. “PPIs are rarely discontinued,” and may be an underappreciated contributor to AKI by causing interstitial nephritis in some patients.

The prospective study included 5,060 adults admitted with a diagnosis of stage 1 AKI at any of four Yale-affiliated teaching hospitals who were also taking agents from at least one of the three targeted drug classes at the time of admission. Clinicians caring for 2,532 of these patients received an alert about the AKI diagnosis and use of the questionable medications, while those caring for the 2,528 control patients received no alert and delivered usual care.

The study excluded patients with higher-risk profiles, including those with extremely elevated serum creatinine levels at admission (4.0 mg/dL or higher), those recently treated with dialysis, and patients with end-stage kidney disease.

The study had two primary outcomes. One measured the impact of the intervention on stopping the targeted drugs. The second assessed the clinical effect of the intervention on progression of AKI to a higher stage, need for dialysis, or death during either the duration of hospitalization or during the first 14 days following randomization.
 

Overall, a 9% relative increase in discontinuations

In general, the intervention had a modest but significant effect on cessation of the targeted drug classes within 24 hours of sending the alert.

Overall, there was about a 58% discontinuation rate among controls and about a 62% discontinuation rate among patients managed using the alerts, a significant 9% relative increase in any drug discontinuation, Dr. Wilson reported.

Discontinuations of NSAIDs occurred at the highest rate, in about 80% of patients in both groups, and the intervention showed no significant effect on stopping agents from this class. Discontinuations of RAAS inhibitors showed the largest absolute difference in between-group effect, about a 10–percentage point increase that represented a significant 14% relative increase in stopping agents from this class. Discontinuations of PPIs occurred at the lowest rate, in roughly 20% of patients, but the alert intervention had the greatest impact by raising the relative rate of stopping by a significant 26% compared with controls.

Analysis of the effect of the intervention on the combined clinical outcome showed a less robust impact. The alerts produced no significant change in the clinical outcome overall, or in the use of NSAIDs or RAAS inhibitors. However, the change in use of PPIs following the alerts significantly linked with a 12% relative drop in the incidence of the combined clinical endpoint of progression of AKI to a higher stage, need for dialysis, or death.

The results were consistent across several prespecified subgroups based on parameters such as age, sex, and race, but these analyses showed a signal that the alerts were most helpful for patients who had serum creatinine levels at admission of less than 0.5 mg/dL.

Dr. Wilson speculated that the alerts might have been especially effective for these patients because their low creatinine levels might otherwise mask AKI onset.

A safety analysis showed no evidence that the alert interventions and drug cessations increased the incidence of any complications.
 

PPIs may distinguish ‘sicker’ patients

Dr. Wilson cited two potential explanations for why the tested alerts appeared most effective for patients taking a PPI at the time of admission. One is that PPIs are underappreciated as a contributor to AKI, a possibility supported by the low rates of discontinuation in both the control and intervention groups.

In addition, treatment with a PPI may be a marker of “sicker” patients who may have more to gain from quicker identification of their AKI. For example, 28% of the patients who were taking a PPI at admission were in the ICU when they entered the study compared with a 14% rate of ICU care among everyone else.

PPIs were also the most-used targeted drug class among enrolled patients, used by 65% at baseline, compared with 53% who were taking a RAAS inhibitor and about 31% who were taking an NSAID. About 6% of enrolled patients were taking agents from all three classes at baseline, and 36% were on treatment with agents from two of the classes.

The next step is to assess adding more refinement to the alert process, Dr. Wilson said. He and his associates are now running a study in which an AKI alert goes to a “kidney action team” that includes a trained clinician and a pharmacist. The team would review the patient who triggered the alert and quickly make an individualized assessment of the best intervention for resolving the AKI.

The study received no commercial funding. Dr. Wilson has received research funding from AstraZeneca, Boehringer Ingelheim, Vifor, and Whoop. Dr. Griffin has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.